U.S. patent application number 17/150668 was filed with the patent office on 2021-11-11 for immunotherapy of cancer.
This patent application is currently assigned to Phio Pharmaceuticals Corp.. The applicant listed for this patent is Phio Pharmaceuticals Corp.. Invention is credited to Alexey Eliseev, Taisia Shmushkovich, Alexey Wolfson.
Application Number | 20210348166 17/150668 |
Document ID | / |
Family ID | 1000005738992 |
Filed Date | 2021-11-11 |
United States Patent
Application |
20210348166 |
Kind Code |
A1 |
Wolfson; Alexey ; et
al. |
November 11, 2021 |
IMMUNOTHERAPY OF CANCER
Abstract
Immunogenic modulators and compositions comprising
oligonucleotide agents capable of inhibiting suppression of immune
response by reducing expression of one or more gene involved with
an immune response suppression mechanism.
Inventors: |
Wolfson; Alexey;
(Westborough, MA) ; Eliseev; Alexey; (Boston,
MA) ; Shmushkovich; Taisia; (Newton, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Phio Pharmaceuticals Corp. |
Marlborough |
MA |
US |
|
|
Assignee: |
Phio Pharmaceuticals Corp.
Marlborough
MA
|
Family ID: |
1000005738992 |
Appl. No.: |
17/150668 |
Filed: |
January 15, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15100536 |
May 31, 2016 |
10934550 |
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PCT/US14/68244 |
Dec 2, 2014 |
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17150668 |
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61910728 |
Dec 2, 2013 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C12N 15/1137 20130101;
C12N 2320/50 20130101; C12N 2310/17 20130101; C12N 15/1135
20130101; C12N 2320/32 20130101; C12N 2310/321 20130101; C12N
15/117 20130101; A61K 2039/5156 20130101; Y02A 50/30 20180101; C12N
15/1138 20130101; C12N 2320/31 20130101; A61K 39/00 20130101; C12N
2310/14 20130101; A61K 2039/5154 20130101; C12N 2310/3515 20130101;
C12N 15/113 20130101 |
International
Class: |
C12N 15/117 20060101
C12N015/117; A61K 39/00 20060101 A61K039/00; C12N 15/113 20060101
C12N015/113 |
Claims
1. An immune modulator comprising an sdRNA, wherein the sdRNA
comprises a guide strand and a passenger strand, wherein the guide
strand is about 19-25 nucleotides long, and the passenger strand is
about 10-19 nucleotides long, wherein the sdRNA includes a double
stranded region and a single stranded region, wherein the single
stranded region includes 5-9 phosphorothioate modifications,
wherein the sdRNA is chemically modified, including at least one
2'-O-methyl modification or 2'-fluoro modification, and wherein the
sdRNA is capable of suppressing expression of HAVCR2.
2. An immunogenic composition comprising an sdRNA, wherein the
sdRNA comprises a guide strand and a passenger strand, wherein the
guide strand is about 19-25 nucleotides long, and the passenger
strand is about 10-19 nucleotides long, wherein the sdRNA includes
a double stranded region and a single stranded region, wherein the
single stranded region includes 5-9 phosphorothioate modifications,
wherein the sdRNA is chemically modified, including at least one
2'-O-methyl modification or 2'-fluoro modification, wherein the
sdRNA is capable of suppressing expression of HAVCR2, and wherein
the immunogenic composition further comprises immune cells modified
by the sdRNA to suppress expression of HAVCR2.
3. The immunogenic composition of claim 2, wherein the immune cells
within the composition are further modified to suppress expression
of a plurality of immune checkpoint genes.
4. The immunogenic composition of claim 2, wherein said cells are
modified to suppress expression of at least one immune checkpoint
gene, and at least one gene selected from the group consisting of:
an anti-apoptosis gene, a cytokine receptor gene, and a regulator
gene.
5-8. (canceled)
9. The immunogenic composition of claim 3, wherein said modified
cells further comprise one or more sdRNA capable of suppressing
expression of at least one target gene selected from the group
consisting of: CTLA4, PD1/PDCD1, TGFBR1, TGFRBR2, IL10RA, TP53,
BAX, BAK1, CASP8, ADORA2A, LAG3, CCL17, CCL22, DLL2, FASLG, CD274,
IDO1, ILIORA, JAG1, JAG2, MAPK14, SOCS1, STAT3, TNFAIP3, TYRO3,
BTLA, KIR, B7-H3 receptor, and B7-H4 receptor.
10. The immunogenic composition of claim 9, wherein said cells are
selected from the group consisting of T-cells, NK-cells,
antigen-presenting cells, dendritic cells, stem cells, induced
pluripotent stem cells, and/or stem central memory T-cells.
11. The immunogenic composition of claim 9, wherein said cells are
T-cells comprising one or more transgene expressing high affinity
T-cell receptors (TCR) and/or chimeric antibody-T-cell receptors
(CAR).
12. (canceled)
13. The immunogenic composition of claim 9, wherein said cells
comprise one or more sdRNA targeting one or more anti-apoptotic
genes selected from the group consisting of BAX, BAC, TP53, and
Casp8.
14. (canceled)
15. The immunogenic composition of claim 9, wherein said sdRNA
comprises at least one 2'-O-methyl modification and/or at least one
2'-O-Fluoro modification, and at least one phosphorothioate
modification.
16. The immunogenic composition of claim 9, wherein said sdRNA
comprises at least one hydrophobic modification.
17. The immunogenic composition of claim 9, wherein said sdRNA is
modified to comprises at least one cholesterol molecule.
18. The immunogenic composition of claim 9, wherein said sdRNA
targets a sequence selected from SEQ ID NOs: 1-360 and
381-1000.
19. A method of producing the immunogenic composition of claim 3,
said method comprising transforming at least one cell with one or
more sdRNA capable of targeting and suppressing expression of one
or more immune target genes, wherein at least one sdRNA interferes
with HAVCR2 expression.
20. The method of claim 19, wherein the at least one cell comprises
an sdRNA that inhibits expression of one or more genes selected
from the group consisting of: CTLA4, PD1/PDCD1, TGFBR1, TGFRBR2,
IL10RA, TP53, BAX, BAK1, CASP8, ADOARA2A, LAG3, CCL17, CCL22, DLL2,
FASLG, CD274, IDO1, ILIORA, JAG1, JAG2, MAPK14, SOCS1, STAT3,
TNFAIP3, TYRO3, BTLA, KIR, B7-H3 receptor, and B7-H4 receptor.
21. The method of claim 19, wherein said cells are selected from
the group consisting of T-cells, NK-cells, antigen-presenting
cells, dendritic cells, stem cells, induced pluripotent stem cells,
and/or stem central memory T-cells.
22-24. (canceled)
25. A method for treating a subject having proliferative disease or
infectious disease, the method comprising administering to the
subject the immune modulator of claim 1.
26. The method of claim 25, wherein said proliferative disease is
cancer.
27. The method of claim 25, wherein said infectious disease is a
pathogen infection.
28. (canceled)
29. The immune modulator of claim 1, wherein at least one sdRNA
targets a sequence selected from SEQ ID NOs: 361-380.
30. The immunogenic composition of claim 2, wherein at least one
sdRNA targets a sequence selected from SEQ ID NOs: 361-380.
Description
CROSS REFERENCE
[0001] This application claims priority to U.S. Provisional
Application No. 61/910,728, filed Dec. 2, 2013, herein incorporated
by reference in its entirety.
TECHNICAL FIELD
[0002] The present invention relates to immunogenic compositions,
method of making immunogenic compositions, and methods of using
immunogenic compositions for the treatment of cell proliferative
disorders or infectious disease, including, for example, cancer and
autoimmune disorders.
[0003] More particularly, the invention provides cells that are
treated with oligonucleotides specifically designed to modulate
expression of target genes involved in tumor immune resistance
mechanisms.
BACKGROUND
[0004] Immunotherapy is the "treatment of disease by inducing,
enhancing, or suppressing an immune response". Immunotherapies
designed to elicit or amplify an immune response are activation
immunotherapies, while immunotherapies that reduce or suppress
immune response are classified as suppression immunotherapies.
[0005] Immunotherapy of cancer has become increasingly important in
clinical practice over recent decades. The primary approach in
today's standard of care is passive immunotherapy through the use
of recombinant monoclonal antibodies (mAbs). MAbs act through a
mechanisms relevant to the body's own humoral immune response, by
binding to key antigens involved in the tumor development and
causing moderate forms of cell-mediated immunity, such as
antibody-dependent cell-mediated cytotoxicity (ADCC).
[0006] Another group of emerging immunotherapeutic approaches is
based on the administration of cells capable of destroying tumor
cells. The administered cells may be the patient's own
tumor-infiltrating lymphocytes (TIL), isolated and expanded
ex-vivo. In some cases, TIL are capable of recognizing a variety of
tumor associated antigens (TAA), while in other cases TIL can be
reactivated and expanded in vitro to recognize specific antigens.
The TIL-based therapeutic approaches are commonly referred to as
"adoptive cell transfer" (ACT).
[0007] Further developments of ACT involve genetic modifications of
T-cells to express receptors that recognize specific
tumor-associated antigens (TAA). Such modifications may induce the
expression of a specific T-cell receptor (TCR) or of a chimeric
antigen receptor (CAR) consisting of TAA-specific antibody fused to
CD3/co-stimulatory molecule transmembrane and cytoplasmic
domains.
[0008] The ACT methods may also be considered as passive
immunotherapeutic approaches in that they act directly on the tumor
cells without invoking an extended immune response. However, unlike
mAbs, ACT agents are capable of fully destroying the tumor cells,
as opposed to the blockade of selected receptors and moderate
cellular responses such as ADCC.
[0009] There is ongoing development of numerous methods of active
immunotherapy, which restore the ability of body's own immune
system to generate antitumor response. Active immunotherapeutic
agents are often called therapeutic cancer vaccines, or just cancer
vaccines. Many cancer vaccines are currently in clinical trials,
and sipuleucell-T has recently become the first such vaccine
approved by the United States FDA.
[0010] There are several classes of cancer vaccines using different
antigens and different mechanisms of generating cell-mediated
immune response. One class of vaccines is based on peptide
fragments of antigens selectively expressed by tumor cells. The
peptides are administered alone or in combination with
immune-stimulatory agents, which may include adjuvants and
cytokines, such as granulocyte-macrophage colony-stimulating factor
(GM-CSF).
[0011] Another class of cancer vaccines is based on modified (e.g.
sub-lethally irradiated) tumor cells used as antigens, also in
combinations with immunostimulatory agents. Vaccines of this type
currently in clinical trials are based both on autologous (e.g.
OncoVAX, LipoNova) and allogeneic (e.g. Canvaxin, Onyvax-P, GVAX)
tumor cell lines.
[0012] Yet another class of cancer vaccines uses dendritic cells.
By their nature, dendritic cells (DC) are "professional"
antigen-presenting cells capable of generating of a strong
antigen-dependent cell-mediated immune response and eliciting
therapeutic T-cells in vivo. DC-based cancer vaccines usually
comprise DCs isolated from patients or generated ex vivo by
culturing patient's hematopoietic progenitor cells or monocytes.
DCs are further loaded with tumor antigens and sometimes combined
with immune-stimulating agents, such as GM-CSF. A large number of
DC-vaccines are now in clinical trials, and the first FDA-approved
vaccine sipuleucell-T is based on DC.
[0013] Mechanisms of Immunosuppression and Therapeutic Approaches
to its Mitigation
[0014] One of the key physiologic functions of the immune system is
to recognize and eliminate neoplastic cells, therefore an essential
part of any tumor progression is the development of immune
resistance mechanisms. Once developed, these mechanisms not only
prevent the natural immune system from effecting the tumor growth,
but also limit the efficacy of any immunotherapeutic approaches to
cancer. An important immune resistance mechanism involves
immune-inhibitory pathways, sometimes referred to as immune
checkpoints. The immune-inhibitory pathways play particularly
important role in the interaction between tumor cells and CD8+
cytotoxic T-lymphocytes, including ACT therapeutic agents. Among
important immune checkpoints are inhibitory receptors expressed on
the T-cell surface, such as CTLA-4, PD1 and LAG3, among others.
[0015] The importance of the attenuation of immune checkpoints has
been recognized by the scientific and medical community. One way to
mitigate immunosuppression is to block the immune checkpoints by
specially designed agents. The CTLA-4-blocking-antibody,
ipilimumab, has recently been approved by the FDA. Several
molecules blocking PD1 are currently in clinical development.
[0016] Immunosuppression mechanisms also negatively affect the
function of dendritic cells and, as a consequence, the efficacy of
DC-based cancer vaccines. Immunosuppressive mechanisms can inhibit
the ability of DC to present tumor antigens through the MHC class I
pathway and to prime naive CD8+ T-cells for antitumor immunity.
Among the important molecules responsible for the immunosuppression
mechanisms in DC are ubiquitin ligase A20 and the broadly
immune-suppressive protein SOCS1.
[0017] The efficacy of immunotherapeutic approaches to cancer can
be augmented by combining them with inhibitors of immune
checkpoints. Numerous ongoing preclinical and clinical studies are
exploring potential synergies between cancer vaccines and other
immunotherapeutic agents and checkpoint blocking agents, for
example, ipilimumab. Such combination approaches have the potential
to result in significantly improved clinical outcomes.
[0018] However, there are a number of drawbacks of using cancer
immunotherapeutic agents in combination with checkpoint inhibitors.
For example, immune checkpoint blockade can lead to the breaking of
immune self-tolerance, thereby inducing a novel syndrome of
autoimmune/auto-inflammatory side effects, designated "immune
related adverse events," mainly including rash, colitis, hepatitis
and endocrinopathies (Corsello, et al. J. Clin. Endocrinol. Metab.,
2013, 98:1361).
[0019] Reported toxicity profiles of checkpoint inhibitors are
different than the toxicity profiles reported for other classes of
oncologic agents. Those involve inflammatory events in multiple
organ systems, including skin, gastrointestinal, endocrine,
pulmonary, hepatic, ocular, and nervous system. (Hodi, 2013, Annals
of Oncology, 24: Suppl, i7).
[0020] In view of the above, there is a need for new cancer
therapeutic agents that can be used in combination with checkpoint
inhibitors as well as other classes of oncolytic agents without
risk of adverse inflammatory events in multiple organ systems
previously reported for checkpoint inhibitors. The
immunotherapeutic cells of the invention, prepared by treating
cells with a combination oligonucleotide agents targeting genes
associated with tumor or infections disease resistance mechanisms,
as well as methods of producing such therapeutic cells and methods
of treating disease with the produced therapeutic cells, satisfy
this long felt need.
SUMMARY OF EMBODIMENTS OF THE INVENTION
[0021] The efficacy of immunotherapeutic approaches to cell
proliferation disorders and infectious diseases can be augmented by
combining them with inhibitors of immune checkpoints. Numerous
synergies between cancer vaccines and other immunotherapeutic
agents and checkpoint blocking agents provide opportunities for
combination approaches that may significantly improve clinical
outcomes for example, in proliferative cell disorders and immune
diseases.
[0022] Various embodiments of the inventions disclosed herein
include compositions comprising therapeutic cells obtained by
treating cells ex vivo with oligonucleotides to modulate expression
of target genes involved in immune suppression mechanisms. The
oligonucleotide agent may be an antisense oliogonucleotide (ASO),
including locked nucleic acids (LNAs), methoxyethyl gapmers, and
the like, or an siRNA, miRNA, miRNA-inhibitor, morpholino, PNA, and
the like. The oligonucleotide is preferably a self-delivered (sd)
RNAi agent. The oligonucleotides may be chemically modified, for
example, including at least one 2-O-methyl modification, 2'-Fluro
modification, and/or phosphorothioate modification. The
oligonucleotides may include one or more hydrophobic modification,
for example, one or more sterol, cholesterol, vitamin D, Naphtyl,
isobutyl, benzyl, indol, tryptophane, or phenyl hydrophobic
modification. The oligonucleotide may be a hydrophobically-modified
siRNA-antisense hybrid. The oligonucleotides may be used in
combination with transmembrane delivery systems, such as delivery
systems comprising lipids.
[0023] In an embodiment, the cells are obtained and/or derived from
a cancer or infectious disease patient, and may be, for example,
tumor infiltrating lymphocytes (TIL) and/or T-cells, antigen
presenting cells such as dendritic cells, natural killer cells,
induced-pluripotent stem cells, stem central memory T-cells, and
the like. The T-cells and NK-cells are preferably genetically
engineered to express high-affinity T-Cell receptors (TCR) and/or
chimeric antibody or antibody-fragment--T-Cell receptors (CAR). In
an embodiment, the chimeric antibody/antibody fragment is
preferably capable of binding to antigens expressed on tumor cells.
Immune cells may be engineered by transfection with plasmid, viral
delivery vehicles, or mRNAs.
[0024] In an embodiment, the chimeric antibody or fragment is
capable of binding CD19 receptors of B-cells and/or binding to
antigens expressed on tumors, such as melanoma tumors. Such
melanoma-expressed antigens include, for example, GD2, GD3,
HMW-MAA, VEGF-R2, and the like.
[0025] Target genes identified herein for modification include:
cytotoxic T-cell antigen 4 (CTLA4), programmed cell death protein 1
(PD1), tumor growth factor receptor beta (TGFR-beta), LAG3, TIM3,
and adenosine A2a receptor; anti-apoptotic genes including, but not
limited to: BAX, BAC, Casp8, and P53; A20 ubiquitine ligase
(TNFAIP3, SOCS1 (suppressor of cytokine signaling), IDO
(indolamine-2,3-dioxygenase; tryptophan-degrading enzyme), PD-L1
(CD274)(surface receptor, binder to PD1 on Tcells), Notch ligand
Deltal (DLL1), Jagged 1, Jagged 2, FasL (pro-apoptotic surface
molecule), CCL17, CCL22 (secreted chemokines that attract Treg
cells), IL10 receptor (IL10RA), p38 (MAPK14), STAT3, TNFSF4
(OX40L), MicroRNA miR-155, miR-146a, anti-apoptotic genes including
but not limited to BAX, BAC, Casp8 and P53, and the like genes, and
combinations thereof. Representative target sequences are listed in
Table 1.
[0026] The engineered therapeutic cells are treated with RNAi
agents designed to inhibit expression of one or more of the
targeted genes. The RNAi agent may comprise a guide sequence that
hybridizes to a target gene and inhibits expression of the target
gene through an RNA interference mechanism, where the target region
is selected from the group listed in Table 1. The RNA agent can be
chemically modified, and preferably includes at least one
2'-O-methyl, 2'-O-Fluoro, and/or phosphorothioate modification, as
well as at least one hydrophobic modification such as cholesterol,
and the like.
[0027] The immunogenic compositions described herein are useful for
the treatment of proliferative disorders, including cancers, and/or
infectious disease and are produced by the ex-vivo treatment of
cells with oligonucleotides to modulate the expression of target
genes involved in tumor immune resistance mechanisms. The ex vivo
treatment of cells includes administering to the cells an
oligonucleotide capable of targeting and inhibiting expression of a
gene involved in a tumor suppressor mechanism, such as the genes
listed in Table 1. The oligonucleotide can be used in combination
with a transmembrane delivery system that may comprise one or more
of: lipid(s) and vector, such as a viral vector.
[0028] The invention includes a method of treating a cell
proliferative disorder or infectious disease by administering to a
subject in need thereof, an immunogenic composition comprising
cells that have been treated with one or more oligonucleotide to
modulate the expression of one or more target gene involved in
tumor immune resistance mechanisms, for example, one or more of the
target genes of Table 1.
[0029] The invention preferably includes immunogenic cells treated
with a plurality of oligonucleotide agents targeting a combination
of target genes described herein. The combination may target a
plurality of suppressor receptor genes, cytokine receptor genes,
regulatory genes, and/or apoptotic factors in order to inhibit
tumor immune resistance mechanisms.
[0030] The present invention is directed to novel immunotherapeutic
cells, methods of generating the immunotherapeutic cells, and
therapeutic methods employing such cells.
[0031] A new method of immune checkpoint inhibition is described
herein, applicable to a broad variety of cell-based
immunotherapies, including, but not limited to adaptive cell
transfer, for example, based on TIL, TCR, CAR, and other cell
types, as well as dendritic cell-based cancer vaccines.
Self-deliverable RNAi technology provides efficient transfection of
short oligonucleotides in any cell type, including immune cells,
providing increased efficacy of immunotherapeutic treatments. In
addition, the activated immune cells can be protected by preventing
apoptosis via inhibition of key activators of the apoptotic
pathway, such as BAC, BAX, Casp8, and P53, among others.
[0032] The activated immune cells modified by oligonucleotide
transfer for a single therapeutic agent for administration to a
subject, providing a number of advantages as compared to separately
administered combinations of vaccines and immunotherapeutics and
separately administered checkpoint inhibitors. These advantages
include lack of side effects associated with the checkpoint
inhibitors in a single therapeutic agent (activated immune cells
modified by oligonucleotides targeting immune resistance
genes).
[0033] The claimed immunotherapeutic cells, method of producing
immunotherapeutic cells by introduction of oligonucleotide
molecules targeting immune resistance pathways, and methods of
treating proliferative and infectious disease, improves upon any
known immunotherapeutic cells and methods of producing
immunotherapeutic cells because it provides: [0034] 1) a single
therapeutic composition providing a combination of checkpoint
inhibitors and other immune resistance mechanism inhibitors; [0035]
2) with reduced toxicity; and [0036] 3) increased efficacy as
compared with other compositions.
BRIEF DESCRIPTION OF THE FIGURES
[0037] The foregoing features of embodiments will be more readily
understood by reference to the following detailed description,
taken with reference to the accompanying drawings, in which:
[0038] FIG. 1 is a schematic diagram showing the structure of an
sdRNA molecule.
[0039] FIG. 2 is a graph showing sdRNA-induced silencing of GAPDH
and MAP4K4 in HeLa cells.
[0040] FIG. 3 is a graph showing sdRNA-induced knock-down of
multiple targets using sdRNA agents directed to three genes in
NK-92 cells.
[0041] FIG. 4 is a graph showing the knock-down of gene expression
in Human Primary T cells by sdRNA agents targeting TP53 and
MAP4K4.
[0042] FIG. 5 is a graph showing sdRNA-induced knock-down of CTLA4
and PD1 in Human Primary T cells.
[0043] FIG. 6 is a graph showing the reduction of PDCD1 and CTLA-4
surface expression by sdRNA in Human Primary T cells.
[0044] FIG. 7 is a graph showing MAP4K4-cy3 sdRNA delivery into T
and B cells in human PBMCs.
DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS
[0045] The invention is defined by the claims, and includes
oligonucleotides specifically designed and selected to reduce
and/or inhibit expression of suppressors of immune resistance
(inhibitory oligonucleotides), compositions comprising cells
modified by treatment with such inhibitory oligonucleotides,
methods of making such compositions, and methods of using the
compositions to treat proliferation and/or infectious diseases. In
particular, cells are treated with a combination of oligonucleotide
agents, each agent particularly designed to interfere with and
reduce the activity of a targeted immune suppressor.
[0046] Preferably, the combination of oligonucleotide agents
targets multiple immune suppressor genes selected from checkpoint
inhibitor genes such as CTLA4, PD-1/PD-1L, BTLA (B and T-lymphocyte
attenuator), KIR (killer immunoglobulin-like receptors), B7-H3,
B7-H4 receptors, and TGF beta type 2 receptor; cytokine receptors
that inactivate immune cells, such as TGF-beta receptor A and IL-10
receptor; regulatory genes/transcription factors modulating
cytokine production by immune cells, such as STAT-3 and P38,
miR-155, miR-146a; and apoptotic factors involved in cascades
leading to cell death, such as p53 and Cacp8.
[0047] Most preferably the oligonucleotide agent is a
self-deliverable RNAi agent, which is a hydrophobically modified
siRNA-antisense hybrid molecule, comprising a double-stranded
region of about 13-22 base pairs, with or without a 3'-overhang on
each of the sense and antisense strands, and a 3' single-stranded
tail on the antisense strand of about 2-9 nucleotides. The
oligonucleotide contains at least one 2'-O-Methyl modification, at
least one 2'-O-Fluoro modification, and at least one
phosphorothioate modification, as well as at least one hydrophobic
modification selected from sterol, cholesterol, vitamin D, napthyl,
isobutyl, benzyl, indol, tryptophane, phenyl, and the like
hydrophobic modifiers (see FIG. 1). The oligonucleotide may contain
a plurality of such modifications.
Definitions
[0048] As used in this description and the accompanying claims, the
following terms shall have the meanings indicated, unless the
context requires otherwise:
[0049] Proliferative disease, as used herein, includes diseases and
disorders characterized by excessive proliferation of cells and
turnover of cellular matrix, including cancer, atherlorosclerosis,
rheumatoid arthritis, psoriasis, idiopathic pulmonary fibrosis,
scleroderma, cirrhosis of the liver, and the like. Cancers include
but are not limited to, one or more of: small cell lung cancer,
colon cancer, breast cancer, lung cancer, prostate cancer, ovarian
cancer, pancreatic cancer, melanoma, hematological malignancy such
as chronic myeloid leukemia, and the like cancers where
immunotherapeutic intervention to suppress tumor related immune
resistance is needed.
[0050] Immune target genes can be grouped into at least four
general categories: (1) checkpoint inhibitors; (2) cytokine
receptors that inactivate immune cells, (3) anti-apoptotic genes;
and (4) regulator genes, for example, transcription factors.
[0051] Immune Checkpoint inhibitors (ICI), as used herein, include
immunotherapeutic agents that bind to certain checkpoint proteins,
such as cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed
death-1 (PD-1) and its ligand PD-L1 to block and disable inhibitory
proteins that prevent the immune system from attacking diseased
cells such as cancer cells, liberating tumor-specific T cells to
exert their effector function against tumor cells.
[0052] Tumor related immune resistance genes, as used herein,
include genes involved in checkpoint inhibition of immune response,
such as CTLA-4 and PD-1/PD-L1; TGF-beta, LAG3, Tim3, adenosine A2a
receptor;
[0053] Regulator genes, as used herein, include transcription
factors and the like that modulate cytokine production by immune
cells, and include p38, STAT3, microRNAs miR-155, miR-146a;
[0054] Anti-apoptotic genes, as used herein, include BAX, BAC,
Casp8, P53 and the like; and combinations thereof.
[0055] Infectious diseases, as used herein, include, but are not
limited to, diseases caused by pathogenic microorganisms,
including, but not limited to, one or more of bacteria, viruses,
parasites, or fungi, where immunotherapeutic intervention to
suppress pathogen related immune resistance and/or overactive
immune response.
[0056] Immunogenic composition, as used herein, includes cells
treated with one or more oligonucleotide agent, wherein the cells
comprise T-cells. The T-cells may be genetically engineered, for
example, to express high affinity T-cell receptors (TCR), chimeric
antibody--T-cell receptors (CAR), where the chimeric antibody
fragments are capable of binding to CD19 receptors of B-cells
and/or to antigens expressed on tumor cells. In one embodiment, the
chimeric antibody fragments bind antigens expressed on melanoma
tumors, selected from GD2, GD3, HMW-MAA, and VEGF-R2.
[0057] Immunogenic compositions described herein include cells
comprising antigen-presenting cells, dendritic cells, engineered
T-cells, natural killer cells, stem cells, including induced
pluripotent stem cells, and stem central memory T-cells. The
treated cell also comprises one or a plurality of oligonucleotide
agents, preferably sdRNAi agents specifically targeting a gene
involved in an immune suppression mechanism, where the
oligonucleotide agent inhibits expression of said target gene.
[0058] In one embodiment, the target gene is selected from A20
ubiquitin ligase such as TNFAIP3, SOCS1 (suppressor of cytokine
signaling), Tyro3/Axl/Mer (suppressors of TLR signaling), IDO
(indolamine-2,3-dioxygenase, tryptophan-degrading enzyme),
PD-L1/CD274 (surface receptor, binds PD1 on T-cells), Notch ligand
Delta (DLL1), Jagged 1, Jagged 2, FasL (pro-apoptotic surface
molecule), CCL17, CCL22 (secreted chemokines that attract Treg
cells), IL-10 receptor (IL10Ra), p38 (MAPK14), STAT3, TNFSF4
(OX40L), microRNA miR-155, miR-146a, anti-apoptotic genes,
including but not limited to BAX, BAC, Casp8, and P53; and
combinations thereof.
[0059] Particularly preferred target genes are those shown in Table
1.
[0060] Ex-vivo treatment, as used herein, includes cells treated
with oligonucleotide agents that modulate expression of target
genes involved in immune suppression mechanisms. The
oligonucleotide agent may be an antisense oligonucleotide,
including, for example, locked nucleotide analogs, methyoxyethyl
gapmers, cyclo-ethyl-B nucleic acids, siRNAs, miRNAs, miRNA
inhibitors, morpholinos, PNAs, and the like. Preferably, the
oligonucleotide agent is an sdRNAi agent targeting a gene involved
in an immune suppression mechanism. The cells treated in vitro by
the oligonucleotide agent may be immune cells expanded in vitro,
and can be cells obtained from a subject having a proliferative or
infectious disease. Alternatively, the cells or tissue may be
treated in vivo, for example by in situ injection and/or
intravenous injection.
[0061] Oligonucleotide or oligonucleotide agent, as used herein,
refers to a molecule containing a plurality of "nucleotides"
including deoxyribonucleotides, ribonucleotides, or modified
nucleotides, and polymers thereof in single- or double-stranded
form. The term encompasses nucleotides containing known nucleotide
analogs or modified backbone residues or linkages, which are
synthetic, naturally occurring, and non-naturally occurring, which
have similar binding properties as the reference nucleic acid, and
which are metabolized in a manner similar to the reference
nucleotides. Examples of such analogs include, without limitation,
phosphorothioates, phosphoramidates, methyl phosphonates,
chiral-methyl phosphonates, 2-O-methyl ribonucleotides,
peptide-nucleic acids (PNAs).
[0062] Nucleotide, as used herein to include those with natural
bases (standard), and modified bases well known in the art. The
nucleotides can be unmodified or modified at the sugar, phosphate
and/or base moiety, (also referred to interchangeably as nucleotide
analogs, modified nucleotides, non-natural nucleotides,
non-standard nucleotides and other; see, for example, PCT
Publications No. WO 92/07065 and WO 93/15187. Non-limiting examples
of base modifications that can be introduced into nucleic acid
molecules include, hypoxanthine, purine, pyridin-4-one,
pyridin-2-one, phenyl, pseudouracil, 2,4,6-trimethoxy benzene,
3-methyl uracil, dihydrouridine, naphthyl, aminophenyl,
5-alkylcytidines (e.g., 5-methylcytidine), 5-alkyluridines (e.g.,
ribothymidine), 5-halouridine (e.g., 5-bromouridine) or
6-azapyrimidines or 6-alkylpyrimidines (e.g. 6-methyluridine and
pseudouridine), propyne, and others. The phrase "modified bases"
includes nucleotide bases other than adenine, guanine, cytosine,
and uracil, modified for example, at the 1' position or their
equivalents.
[0063] As used herein, the term "deoxyribonucleotide" encompasses
natural and synthetic, unmodified and modified
deoxyribonucleotides. Modifications include changes to the sugar
moiety, to the base moiety and/or to the linkages between
deoxyribonucleotide in the oligonucleotide.
[0064] As used herein, the term "RNA" defines a molecule comprising
at least one ribonucleotide residue. The term "ribonucleotide"
defines a nucleotide with a hydroxyl group at the 2' position of a
.quadrature.-D-ribofuranose moiety. The term RNA includes
double-stranded RNA, single-stranded RNA, isolated RNA such as
partially purified RNA, essentially pure RNA, synthetic RNA,
recombinantly produced RNA, as well as altered RNA that differs
from naturally occurring RNA by the addition, deletion,
substitution and/or alteration of one or more nucleotides.
Nucleotides of the RNA molecules described herein may also comprise
non-standard nucleotides, such as non-naturally occurring
nucleotides or chemically synthesized nucleotides or
deoxynucleotides. These altered RNAs can be referred to as analogs
or analogs of naturally-occurring RNA.
[0065] As used herein, "modified nucleotide" refers to a nucleotide
that has one or more modifications to the nucleoside, the
nucleobase, pentose ring, or phosphate group. For example, modified
nucleotides exclude ribonucleotides containing adenosine
monophosphate, guanosine monophosphate, uridine monophosphate, and
cytidine monophosphate and deoxyribonucleotides containing
deoxyadenosine monophosphate, deoxyguanosine monophosphate,
deoxythymidine monophosphate, and deoxycytidine monophosphate.
Modifications include those naturally-occurring that result from
modification by enzymes that modify nucleotides, such as
methyltransferases.
[0066] Modified nucleotides also include synthetic or non-naturally
occurring nucleotides. Synthetic or non-naturally occurring
modifications in nucleotides include those with 2' modifications,
e.g., 2'-O-methyl, 2'-methoxyethoxy, 2'-fluoro, 2'-allyl,
2'-O-[2-(methylamino)-2-oxoethyl], 4'-thio, 4'-CH2-O-2'-bridge,
4'-(CH2) 2-O-2'-bridge, 2'-LNA, and 2'-O-(N-methylcarbamate) or
those comprising base analogs. In connection with 2'-modified
nucleotides as described for the present disclosure, by "amino" is
meant 2'-NH2 or 2'-O--NH2, which can be modified or unmodified.
Such modified groups are described, for example, in U.S. Pat. Nos.
5,672,695 and 6,248,878.
[0067] As used herein, "microRNA" or "miRNA" refers to a nucleic
acid that forms a single-stranded RNA, which single-stranded RNA
has the ability to alter the expression (reduce or inhibit
expression; modulate expression; directly or indirectly enhance
expression) of a gene or target gene when the miRNA is expressed in
the same cell as the gene or target gene. In one embodiment, a
miRNA refers to a nucleic acid that has substantial or complete
identity to a target gene and forms a single-stranded miRNA. In
some embodiments miRNA may be in the form of pre-miRNA, wherein the
pre-miRNA is double-stranded RNA. The sequence of the miRNA can
correspond to the full length target gene, or a subsequence
thereof. Typically, the miRNA is at least about 15-50 nucleotides
in length (e.g., each sequence of the single-stranded miRNA is
15-50 nucleotides in length, and the double stranded pre-miRNA is
about 15-50 base pairs in length). In some embodiments the miRNA is
20-30 base nucleotides. In some embodiments the miRNA is 20-25
nucleotides in length. In some embodiments the miRNA is 20, 21, 22,
23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length.
[0068] Target gene, as used herein, includes genes known or
identified as modulating the expression of a gene involved in an
immune resistance mechanism, and can be one of several groups of
genes, such as suppressor receptors, for example, CTLA4 and PD1;
cytokine receptors that inactivate immune cells, for example,
TGF-beta receptor, LAG3, Tim3, adenosine A2a receptor, and IL10
receptor; regulatory genes for example, STAT3, p38, mir155 and
mir146a; and apoptosis factors involved in cascades leading to cell
death, for example, P53, Casp8, BAX, BAC, and combinations thereof.
See also preferred target genes listed in Table 1.
[0069] As used herein, small interfering RNA (siRNA), sometimes
known as short interfering RNA or silencing RNA, defines a group of
double-stranded RNA molecules, comprising sense and antisense RNA
strands, each generally of about 1022 nucletides in length,
optionally including a 3' overhang of 1-3 nucleotides. siRNA is
active in the RNA interference (RNAi) pathway, and interferes with
expression of specific target genes with complementary nucleotide
sequences.
[0070] As used herein, sdRNA refers to "self-deliverable" RNAi
agents, that are formed as an asymmetric double-stranded
RNA-antisense oligonucleotide hybrid. The double stranded RNA
includes a guide (sense) strand of about 19-25 nucleotides and a
passenger (antisense) strand of about 10-19 nucleotides with a
duplex formation that results in a single-stranded
phosphorothiolated tail of about 5-9 nucleotides.
[0071] The RNA sequences may be modified with stabilizing and
hydrophobic modifications such as sterols, for example,
cholesterol, vitamin D, naphtyl, isobutyl, benzyl, indol,
tryptophane, and phenyl, which confer stability and efficient
cellular uptake in the absence of any transfection reagent or
formulation. Immune response assays testing for IFN-induced
proteins indicate sdRNAs produce a reduced immunostimulatory
profile as compared other RNAi agents. See, for example, Byrne et
al., December 2013, J. Ocular Pharmacology and Therapeutics,
29(10): 855-864.
Cell-Based Immunotherapeutics
[0072] In general, cells are obtained from subjects with
proliferative disease such as cancer, or an infectious disease such
as viral infection. The obtained cells are treated directly as
obtained or may be expanded in cell culture prior to treatment with
oligonucleotides. The cells may also be genetically modified to
express receptors that recognize specific antigens expressed on the
tumor cell surface (CAR) or intracellular tumor antigens presented
on MHC class I (TCR).
Oligonucleotide Agents
[0073] Antisense Oligonucleotides
[0074] Small interfering RNA (siRNA), sometimes known as short
interfering RNA or silencing RNA, is a double stranded RNA
molecule, generally 19-25 base pairs in length. siRNA is used in
RNA interference (RNAi), where it interferes with expression of
specific genes with complementary nucleotide sequences.
[0075] Double stranded DNA (dsRNA) can be generally used to define
any molecule comprising a pair of complementary strands of RNA,
generally a sense (passenger) and antisense (guide) strands, and
may include single-stranded overhang regions. The term dsRNA,
contrasted with siRNA, generally refers to a precursor molecule
that includes the sequence of an siRNA molecule which is released
from the larger dsRNA molecule by the action of cleavage enzyme
systems, including Dicer.
[0076] sdRNA (self-deliverable) are a new class of covalently
modified RNAi compounds that do not require a delivery vehicle to
enter cells and have improved pharmacology compared to traditional
siRNAs. "Self-deliverable RNA" or sdRNA is a hydrophobically
modified RNA interfering-antisense hybrid, demonstrated to be
highly efficacious in vitro in primary cells and in vivo upon local
administration. Robust uptake and/or silencing without toxicity has
been demonstrated in several tissues including dermal, muscle,
tumors, alveolar macrophages, spinal cord, and retina cells and
tissues. In dermal layer and retina, intradermal and intra-vitreal
injection of sdRNA at mg doses induced potent and long lasting
silencing.
[0077] While sdRNA is a superior functional genomics tool, enabling
RNAi in primary cells and in vivo, it has a relatively low hit rate
as compared to conventional siRNAs. While the need to screen large
number of sequences per gene is not a limiting factor for
therapeutic applications, it severely limits the applicability of
sdRNA technology to functional genomics, where cost effective
compound selection against thousands of genes is required. To
optimize sdRNA structure, chemistry, targeting position, sequence
preferences, and the like, a proprietary algorithm has been
developed and utilized for sdRNA potency prediction. Availability
of sdRNA reagents that are active in all cell types ex vivo and in
vivo enables functional genomics and target
stratification/validation studies.
Proprietary Algorithm
[0078] SdRNA sequences were selected based on a proprietory
selection algorithm, designed on the basis of a functional screen
of over 500 sdRNA sequences in the luciferase reporter assay of
HeLa cells. Regression analysis of was used to establish a
correlation between the frequency of occurrence of specific
nucleotide and modification at any specific position in sdRNA
duplex and its functionality in gene suppression assay. This
algorithm allows prediction of functional sdRNA sequences, defined
as having over 70% knockdown at 1 .mu.M concentration, with a
probability over 40%.
[0079] Table 1 shows predictive gene targets identified using the
proprietary algorithm and useful in the cellular immunotherapeutic
compositions and methods described herein.
Delivery of RNAi Agents
[0080] BTLA (B and T-lymphocyte attenuator), KIR (killer
immunoglobulin-like receptors), B7-H3 and B7-H4 receptors and
TGFbeta type 2 receptor; Applic BTLA (B and T-lymphocyte
attenuator), KIR (killer immunoglobulin-like receptors), B7-H3 and
B7-H4 receptors and TGFbeta type 2 receptor; ation of RNAi
technology to functional genomics studies in prim BTLA (B and
T-lymphocyte attenuator), KIR (killer immunoglobulin-like
receptors), B7-H3 and B7-H4 receptors and TGFbeta type 2 receptor;
ary cells and in vivo is limited by requirements to formulate
siRNAs into lipids or use of other cell delivery techniques. To
circumvent delivery problems, the self-deliverable RNAi technology
provides a method of directly transfecting cells with the RNAi
agent, without the need for additional formulations or techniques.
The ability to transfect hard-to-transfect cell lines, high in vivo
activity, and simplicity of use, are characteristics of the
compositions and methods that present significant functional
advantages over traditional siRNA-based techniques. The sdRNAi
technology allows direct delivery of chemically synthesized
compounds to a wide range of primary cells and tissues, both
ex-vivo and in vivo.
[0081] To enable BTLA (B and T-lymphocyte attenuator), KIR (killer
immunoglobulin-like receptors), B7-H3 and B7-H4 receptors and
TGFbeta type 2 receptor; self-delivery, traditional siRNA molecules
require a substantial reduction in size and the introduction of
extensive chemical modifications which are not well tolerated by
RNAi machinery, resulting in extremely low probability of finding
active molecules (low hit rate). In contrast, the sdRNA technology
allows efficient RNAi delivery to primary cells and tissues in
vitro and in vivo, with demonstrated silencing efficiency in
humans.
[0082] The general structure of sdRNA molecules is shown in FIG. 1.
sdRNA are formed as hydrophobically-modified siRNA-antisense
oligonucleotide hybrid structures, and are disclosed, for example
in Byrne et al., December 2013, J. Ocular Pharmacology and
Therapeutics, 29(10): 855-864.
[0083] Oligonucleotide Modifications: 2'-O-Methyl, 2'-O-Fluro,
Phosphorothioate
[0084] The oligonucleotide agents preferably comprise one or more
modification to increase stability and/or effectiveness of the
therapeutic agent, and to effect efficient delivery of the
oligonucleotide to the cells or tissue to be treated. Such
modifications include at least one
[0085] BTLA (B and T-lymphocyte attenuator), KIR (killer
immunoglobulin-like receptors), B7-H3 and B7-H4 receptors and
TGFbeta type 2 receptor; BTLA (B and T-lymphocyte attenuator), KIR
(killer immunoglobulin-like receptors), B7-H3 and B7-H4 receptors
and TGFbeta type 2 receptor; 2'-O-methyl modification, at least one
2'-O-Fluro modification, and at least one diphosphorothioate
modification. Additionally, the oligonucleotide is modified to
include one or more hydrophobic modification selected from sterol,
cholesterol, vitamin D, naphtyl, isobutyl, benzyl, indol,
tryptophane, and phenyl. The hydrophobic modification is preferably
a sterol.
[0086] Delivery of Oligonucleotide Agents to Cells
[0087] The oligonucleotides may be delivered to the cells in
combination with a transmembrane delivery system, preferably
comprising lipids, viral vectors, and the like. Most preferably,
the oligonucleotide agent is a self-delivery RNAi agent, that does
not require any delivery agents.
[0088] Combination Therapy
[0089] Most preferred for this invention, e.g. particular
combinations of elements and/or alternatives for specific needs.
This objective is accomplished by determining the appropriate genes
to be targeted by the oligonucleotide in order to silence immune
suppressor genes and using the proprietary algorithm to select the
most appropriate target sequence.
[0090] It is preferred that the immunotherapeutic cell be modified
to include multiple oligonucleotide agents targeting a variety of
genes involved in immune suppression and appropriate for the
selected target disease and genes. For example, a preferred
immunotherapeutic cell is a T-Cell modified to knock-down both
CTLA-4 and PD-1
[0091] Additional combinations of oligonucleotides to related genes
involved in immune suppression include varied combinations of the
selected target sequences of Table 1.
[0092] BTLA (B and T-lymphocyte attenuator), KIR (killer
immunoglobulin-like receptors), B7-H3 and B7-H4 receptors and
TGFbeta type 2 receptor; (B and T-lymphocyte attenuator), KIR
(killer immunoglobulin-like receptors), B7-H3 and B7-H4 receptors
and TGFbeta type 2 receptor; Preferred BTLA (B and T-lymphocyte
attenuator), KIR (killer immunoglobulin-like receptors), B7-H3 and
B7-H4 receptors and TGFbeta type 2 receptor; therapeutic
combinations include cells engineered to knock down gene expression
of the following target genes: [0093] a) CTLA4 and PD1 [0094] b)
STAT3 and p38 [0095] c) PD1 and BaxPD1, CTLA4, Lag-1, ILM-3, and
TP53 [0096] d) PD1 and Casp8 [0097] e) PD1 and IL10R
[0098] The therapeutic compositions described herein are useful to
treat a subject suffering from a proliferation disorder or
infectious disease. In particular, the immunotherapeutic
composition is useful to treat disease characterized by suppression
of the subjects immune mechanisms. The sdRNA agents described
herein are specifically designed to target genes involved in
diseases-associated immune suppression pathways.
[0099] Methods of treating a subject comprise administering to a
subject in need thereof, an immunogenic composition comprising an
sdRNAi agent capable of inhibiting expression of genes involved in
immune suppression mechanisms, for example, any of the genes listed
in Table 1 or otherwise described herein.
EXAMPLES
[0100] The embodiments of the invention described above are
intended to be merely exemplary; numerous variations and
modifications will be apparent to those skilled in the art. All
such variations and modifications are intended to be within the
scope of the present invention as defined in any appended
claims.
Example 1
Self-Deliverable RNAi Immunotherapeutic Agents
[0101] Immunotherapeutic agents described herein were produced by
treating cells with particular sdRNA agents designed to target and
knock down specific genes involved in immune suppression
mechanisms. In particular, the following cells and cell lines have
been successfully treated with sdRNA and were shown to knock down
at least 70% of targeted gene expression in the specified human
cells.
[0102] These studies demonstrated utility of these immunogenic
agents to suppress expression of target genes in cells normally
very resistant to transfection, and suggests the agents are capable
of reducing expression of target cells in any cell type.
TABLE-US-00001 TABLE 2 Cell Type Target Gene sdRNA target sequence
% Knock Down Primary human T-cells TP53 (P53) GAGTAGGACATACCAGCTTA
(SEQ ID NO: 1001) >70% 2 uM Primary human T-cells MAP4K4
AGAGTTCTGTGGAAGTCTA (SEQ ID NO: 1002) >70% 2 uM Jurkat
T-Iymphoma cells MAP4K4 AGAGTTCTGTGGAAGTCTA (SEQ ID NO: 1003) 100%
1 uM 72h NK-92 cells MAP4K4 AGAGTTCTGTGGAAGTCTA (SEQ ID NO: 1004)
80% 2 uM 72h NK-92 cells PPIB ACAGCAAATTCCATCGTGT (SEQ ID NO: 1005)
>75% 2 uM 72h NK-92 cells GADPH CTGGTAAAGTGGATATTGTT (SEQ ID NO:
1006) >90% 2 uM 72h HeLa Cells MAP4K4 AGAGTTCTGTGGAAGTCTA (SEQ
ID NO: 1007) >80% 2 uM 72h
Example 2
Oligonucleotide Sequences for Inhibiting Expression of Target
Genes
[0103] A number of human genes were selected as candidate target
genes due to involvement in immune suppression mechanisms,
including the following genes shown in Table 3:
TABLE-US-00002 TABLE 3 BAX (NM_004324) BAK1 (NM_001188) CASP8
(NM_001228) ADORA2A (NM_000675) CTLA4 (NM_005214) LAG3 (NM002286)
PDCD1 (NM_NM005018) TGFBR1 (NM-004612) HAVCR2 (NM_032782) CCL17
(NM_002987) CCL22 (NM_002990) DLL2 (NM_005618) FASLG (NM_000639)
CD274 (NM_001267706) IDO1 (NM_002164) IL10RA (NM_001558) JAG1
(NM_000214) JAG2 (NM_002226) MAPK14 (NM_001315) SOCS1 (NM_003745)
STAT3 (NM_003150) TNFA1P3 (NM_006290) TNFSF4 (NM_003326) TYRO2
(NM_006293) TP53 (NM_000546)
[0104] Each of the genes listed above was analyzed using a
proprietary algorithm to identify preferred sdRNA targeting
sequences and target regions for each gene for prevention of
immunosuppression of antigen-presenting cells and T-cells. Results
are shown in Table 1.
Example 3
Knock-Down of Target Gene (GAPDH) by sdRNA in HeLa Cells
[0105] HeLa cells (ATCC CRM-CCL-2) were subcultured 24 hours before
transfection and kept log phase. The efficacy of several GAPDH
sdRNAs was tested by qRT-PCR, including G13 sdRNA listed in the
Table 1.
[0106] Solutions of GAPDH, MAP4K4 (positive control) and NTC
(non-targeting control) sdRNA with twice the required concentration
were prepared in serum-free EMEM medium, by diluting 100 .mu.M
oligonucleotides to 0.2-4 .mu.M.
[0107] The total volume of medium for each oligo concentration
point was calculated as [50 .mu.l/well].times.[number of replicates
for each serum point]. Oligonucleotides were dispensed into a 96
well plate at 50 .mu.l/well.
[0108] Cells were collected for transfection by trypsinization in a
50 ml tube, washed twice with medium containing 10% FBS without
antibiotics, spun down at 200.times.g for 5 minutes at room
temperature and resuspended in EMEM medium containing twice the
required amount of FBS for the experiment (6%) and without
antibiotics. The concentration of the cells was adjusted to
120,000/ml to yield a final concentration of 6,000 cells/50
.mu.l/well. The cells were dispensed at 50 .mu.l/well into the
96-well plate with pre-diluted oligos and placed in the incubator
for 48 hours.
[0109] Gene Expression Analysis in HeLa Cells Using qRT-PCR
[0110] RNA was isolated from transfected HeLa cells using the
PureLink.TM. Pro96 total RNA purification Kit (Ambion, Cat. No.
12173-011A), with Quanta qScript XLT One-Step RT-qPCR ToughMix, ROX
(VWR, 89236672). The isolated RNA was analyzed for gene expression
using the Human MAP4K4-FAM (Taqman Hs0377405 ml) and Human
GAPDH-VIC (Applied Biosystems, Cat. No. 4326317E) gene expression
assays.
[0111] The incubated plate was spun down and washed once with 100
.mu.l/well PBS and lysed with 60 .mu.l/well buffer provided in the
kit. RNA isolation was conducted according to the manufacturer's
instructions, and the RNA was eluted with 100 .mu.l RNase-free
water, and used undiluted for one-step qRT-PCR.
[0112] Dilutions of non-transfected (NT) cells of 1:5 and 1:25 were
prepared for the standard curve using RNase-free water. qRT-PCR was
performed by dispensing 9 .mu.l/well into a low profile PCR plate
and adding 1 .mu.l RNA/well from the earlier prepared RNA samples.
After brief centrifugation, the samples were placed in the
real-time cycler and amplified using the settings recommended by
the manufacturer.
[0113] GAPDH gene expression was measured by qPCR, normalized to
MAP4K4 and plotted as percent of expression in the presence of
non-targeting sdRNA. The results were compared to the normalized
according to the standard curve. As shown in FIG. 2, several sdRNA
agents targeting GAPDH or MAP4K4 significantly reduced their mRNA
levels leading to more than 80-90% knock-down with 1 .mu.M sdRNA.
(See FIG. 2).
Example 4
Silencing of Multiple Targets by sdRNA in NK-92 Cells
[0114] NK-92 cells were obtained from Conqwest and subjected to
one-step RT-PCR analysis without RNA purification using the
FastLane Cell Multiplex Kit (Qiagen, Cat. No. 216513). For
transfection, NK-92 cells were collected by centrifugation and
diluted with RPMI medium containing 4% FBS and IL2 1000 U/ml and
adjusted to1,000,000 cells/ml.
[0115] Multiple sdRNA agents targeting MAP4K4, PPIB or GADPH were
diluted separately in serum-free RPMI medium to 4 .mu.M and
individually aliquoted at 50 .mu.l/well into a 96-well plate. The
prepared cells were then added at 50 .mu.l cells/well to the wells
with either MAP4K4, PPIB or GAPDH sdRNAs. Cells were incubated for
24, 48, or 72 hours.
[0116] At the specified timepoints, the plated transfected cells
were washed once with 100 .mu.l/well PBS and once with FCW buffer.
After removal of supernatant, cell processing mix of 23.5 .mu.l
FCPL and 1.5 .mu.l gDNA wipeout solution was added to each well and
incubated for five minutes at room temperature. Lysates were then
transferred to PCR strips and heated at 75.degree. C. for five
minutes.
[0117] To setup qRT-PCR, the lysates were mixed with QuantiTect
reagents from the FastLane Cell Multiplex Kit and with primer probe
mix for MAP4K4-FAM/GAPDH-VIC or PPIB-FAM/GAPDH-VIC. The following
Taqman gene expression assays were used: human MAP4K4-FAM (Taqman,
Hs00377405_m1), human PPIB-FAM (Taqman, Hs00168719_m1) and human
GAPDH-VIC (Applied Biosystems, cat. No 4326317E).
[0118] A volume of 9 .mu.l/well of each reaction mix was dispensed
into a low profile PCR plate. One .mu.l lysate per well was added
from the previously prepared lysates. The samples were amplified
using the settings recommended by the manufacturer.
[0119] Results shown in FIG. 3 demonstrate significant silencing of
each of the multiple targets, MAP4K4, PPIB, and GADPH by sdRNA
agents transfected into NK-92 cells, including greater than 75%
inhibition of expression of each target within 24 to 72 hours of
incubation.
Example 5
Silencing of TP53 and MAP4K4 by sdRNA in Human Primary T-Cells
[0120] Primary human T-cells were obtained from AllCells (CA) and
cultured in complete RPMI medium containing 1000 IU/ml IL2. Cells
were activated with anti-CD3/CD28 Dynabeads (Gibco, 11131)
according to the manufacturer's instructions for at least 4 days
prior to the transfection. Cells were collected by brief vortexing
to dislodge the beads from cells and separating them using the
designated magnet.
[0121] sdRNA agents targeting TP53 or MAP4K4 were prepared by
separately diluting the sdRNAs to 0.2-4 .mu.M in serum-free RPMI
per sample (well) and individually aliquoted at 100 .mu.l/well of
96-well plate. Cells were prepared in RPMI medium containing 4% FBS
and IL2 2000 U/ml at 1,000,000 cells/ml and seeded at 100
.mu.l/well into the 96-well plate with pre-diluted sdRNAs.
[0122] At the end of the transfection incubation period, the plated
transfected cells were washed once with 100 .mu.l/well PBS and
processed with FastLane Cell Multiplex Kit reagents essentially as
described for the Example 4 and according to the manufacturer's
instructions. Taqman gene expression assays were used in the
following combinations: human MAP4K4-FAM/GAPDH-VIC or human
TP53-FAM (Taqman, Hs01034249_m1)/GAPDH-VIC. A volume of 18
.mu.l/well of each reaction mix was combined with 2 .mu.l lysates
per well from the previously prepared lysates. The samples were
amplified as before (see Example 4).
[0123] Results shown in FIG. 4 demonstrate significant silencing of
both MAP4K4 and TP53 by sdRNA agents transfected into T-cells,
reaching 70-80% inhibition of gene expression with 1-2 .mu.M
sdRNA.
Example 6
Immunotherapeutic Combination of sdRNAs for Treating Melanoma
[0124] Melanomas utilize at least two particular pathways to
suppress immune function of T-cells, and each involves both PD1 and
CTLA4. Melanoma tumors expressing the PD1 ligand, PD1L, can be
targeted with T-cells pretreated ex-vivo with sd-RNAi agents
specifically designed to target PD1 and interfere with PD1
expression. PD1 is also known as PDCD1, and particular targeting
sequences and gene regions identified and predicted to be
particularly functional in sdRNA mediated suppression, are shown in
Table 1 for PDCD1 (NM_005018) and for CTLA4 (NM005214).
[0125] Treatment of melanoma tumors can be effected by providing to
melanoma cells T-cells, such as tumor-infiltrating lymphocytes,
pretreated ex-vivo with a combination of sdRNAs targeting PD1/PDCD1
and CTLA4, for example, targeting one or more of the twenty target
sequences listed for PD1/PDCD1 and/or CTLA4. A combination of
sdRNAs targeting PD1/PDCD1 and FASLG (NM_000639) and/or CTLA4, can
increase T-cell toxicity in tumors expressing both PD1L and
FAS.
[0126] In addition to and in combination with anti-CTLA-4 and
anti-PD1 sdRNAs, T-cells used for the immunotherapy of melanoma can
also be treated with sdRNA targeting other genes implicated in
immunosuppression by the tumor. These receptors include, but are
not limited to TGF-beta type 1 and 2 receptors, BTLA (binder of
herpes virus entry indicator (HVEM) expressed on melanoma cells),
and receptors of integrins expressed by myeloid derived suppressor
cells (MDSC), such as CD11b, CD18, and CD29.
[0127] For tumors whose profile of expressed suppressive proteins
is unknown, any combination of sdRNAs targeting PD1/PDCD1 and any
one of know suppressing receptors may be helpful to reduce immune
suppression and increase therapeutic efficacy.
Example 7
Combination of sdRNAs for Mitigating Immune Cell Suppression
[0128] T-cell or dendritic cell suppression may be modulated by
various cytokines, such as IL10 and/or TGF beta. Suppressing
corresponding receptors in T-cells and dendritic cells may be
beneficial for their activity. For example, providing a combination
of anti-PD1 with anti-IL10R sdRNAs is exptected to mitigate
cytokine induced suppression of T-cells and dendritic cells, as
compared with anti-PD1 alone.
Example 8
Combination of sdRNAs for Mitigating Immune Cell Suppression
[0129] When the mechanism of tumor suppression of immune cells may
be not known, use of sdRNA agents to suppress genes involved in
apoptosis (programmed cell death), such as p53, Casp8 or other gene
activating apoptosis may be beneficial to increase immune cell
activity. Combination of an anti-receptor sdRNAs with sdRNAs
against pro-apoptotic genes can additionally reduce death of immune
cells and thus increase their activity. For example, combination of
anti-PD1 with anti-p53 sdRNAs may additionally protect T-cells from
suppression by blocking activation of apoptosis.
Example 9
Silencing of CTLA-4 and PDCD1 by sdRNA in Human Primary T-Cells
[0130] Primary human T-cells were cultured and activated
essentially as described in Example 5. sdRNA agents targeting PDCD1
and CTLA-4 were prepared by separately diluting the sdRNAs to 0.4-4
.mu.M in serum-free RPMI per sample (well) and aliquoted at 100
.mu.l/well of 96-well plate. Cells were prepared in RPMI medium
containing 4% FBS and IL2 2000 U/ml at 1,000,000 cells/ml and
seeded at 100 .mu.l/well into the 96-well plate with pre-diluted
sdRNAs.
[0131] 72 h later, the transfected cells were washed once with 100
.mu.l/well PBS and processed with FastLane Cell Multiplex Kit
reagents essentially as described for the Example 4 and according
to the manufacturer's instructions. Taqman gene expression assays
were used in the following combinations: human PDCD1-FAM (Taqman,
Hs01550088_m1)/GAPDH-VIC or human CTLA4-FAM (Taqman,
Hs03044418_m1)/GAPDH-VIC. A volume of 18 .mu.l/well of each
reaction mix was combined with 2 .mu.l lysates per well from the
previously prepared lysates. The samples were amplified as before
(see Example 4).
[0132] Results shown in FIG. 5 demonstrate significant silencing of
PDCD1 and CTLA-4 by using combined sdRNA agents delivered to
T-cells, obtaining greater than 60-70% inhibition of gene
expression with 2 .mu.M sdRNA.
Example 10
Reduction of CTLA-4 and PDCD1 Surface Expression by sdRNA in Human
Primary T-Cells
[0133] Primary human T-cells were cultured and activated
essentially as described in Example 5.
[0134] sdRNA agents targeting CTLA-4 or PD1 were separately diluted
to 5 .mu.M in serum-free RPMI per sample (well) and aliquoted at
250 .mu.l/well to 24-well plates. Cells mixed with magnetic beads
were collected and adjusted to 500,000 cells in 250 .mu.l RPMI
medium containing 4% FBS and IL2 2000 IU/ml. Cells were seeded at
250 .mu.l/well to the prepared plate containing pre-diluted sdRNAs.
24 hours later FBS was added to the cells to obtain 10% final
concentration.
[0135] After 72 hours of incubation, the transfected cells were
collected, separated from the activation beads using the magnet, as
described in Example 5. Cells were washed with PBS, spun down and
resuspended in blocking buffer (PBS with 3% BSA) at 200,000
cells/50 .mu.l/sample.
[0136] Antibody dilutions were prepared in the blocking buffer. The
antibodies were mixed in two combinations: anti-PD1/anti-CD3 (1:100
dilutions for both antibodies) and anti-CTLA4/anti-CD3 (10
.mu.l/106 cells for anti-CTLA4; 1:100 for CD3). The following
antibodies were used: rabbit monoclonal [SP7] to CD3 (Abcam,
ab16669); mouse monoclonal [BNI3] to CTLA4 (Abcam, ab33320) and
mouse monoclonal [NAT105] to PD1 (Abcam, ab52587). Cells were mixed
with the diluted antibodies and incubated 30 minutes on ice. Cells
were then washed twice with PBS containing 0.2% Tween-20 and 0.1%
sodium azide.
[0137] Secondary antibodies were diluted in blocking buffer and
mixed together resulting in a final dilution 1:500 for anti-mouse
Cy5 (Abcam, ab97037) and 1:2000 for anti-rabbit Alexa-488 (Abcam,
ab150077). Cells were mixed with the diluted antibodies at 1:1
ratio and incubated 30 minutes on ice. Cells were washed as before,
and diluted in 500 .mu.l PBS per tube. The data was acquired
immediately on the Attune Acoustic Focusing Cytometer (Applied
Biosystems).
[0138] As shown in FIG. 6, sdRNA efficiently reduced surface
expression of CTLA-4 and PD1 in activated Human Primary T
cells.
Example 11
MAP4K4 sdRNA Delivery into CD3- and CD19-Positive Subsets of Human
Peripheral Blood Mononuclear Cells (PBMCs)
[0139] PBMCs were cultured in complete RPMI supplemented with 1.5%
PHA solution and 500 U/ml IL2. For transfection, PBMCs were
collected by centrifugation and diluted with RPMI medium containing
4% FBS and IL2 1000 U/ml and seeded to 24-well plate at 500,000
cells/well.
[0140] MAP4K4 sdRNA labeled with cy3 was added to the cells at 0.1
.mu.M final concentration. After 72 hours of incubation, the
transfected cells were collected, washed with PBS, spun down and
diluted in blocking buffer (PBS with 3% BSA) at 200,000 cells/50
.mu.l/sample.
[0141] Antibody dilutions were prepared in the blocking buffer as
following: 1:100 final dilution anti-CD3 (Abcam, ab16669) and
anti-CD19 at 10 .mu.l/1,000,000 cells (Abcam, ab31947). Cells were
mixed with the diluted antibodies and incubated 30 min on ice.
Cells were then washed twice with PBS containing 0.2% Tween-20 and
0.1% sodium azide.
[0142] Secondary antibodies were diluted in the blocking buffer in
a final dilution 1:500 for anti-mouse Cy5 (Abcam, ab97037) and
1:2000 for anti-rabbit Alexa-488 (Abcam, ab150077). Cells were
mixed with the diluted antibodies at 1:1 ratio and incubated 30 min
on ice. Cells were washed as before, and diluted in 500 .mu.l PBS
per tube. The data was acquired immediately on the Attune Acoustic
Focusing Cytometer (Applied Biosystems).
[0143] FIG. 7 shows efficient transfection over 97% of CD3-positive
(t cells) and over 98% CD19-positive (B-cells) subsets in Human
Peripheral Blood Mononuclear Cells (PBMCs).
TABLE-US-00003 TABLE 1 Targeting sequences and gene regions of
genes targeted with sdRNAs to prevent immunosuppression of
antigen-presenting cells and T-cells. SEQ ID SEQ ID Oligo_count
Oligo_ID targeting sequence NO: Gene_region NO: Accession:
NM_004324 HUGO gene symbol: BAX 1 BAX_NM_004324_
GAATTGCTCAAGTTCATTGA 1 CCTCCACTGCCTCTGGAATTGCTCAAG 21 human_835
TTCATTGATGACCCTCTG 2 BAX_NM_004324_ TTCATCCAGGATCGAGCAGG 2
CTTTTGCTTCAGGGTTTCATCCAGGAT 22 human_ 57 CGAGCAGGGCGAATGGGG 3
BAX_NM_004324_ ATCATCAGATGTGGTCTATA 3 TCTCCCCATCTTCAGATCATCAGATGT
23 human_684 GGTCTATAATGCGTTTTC 4 BAX_NM_004324_
TACTTTGCCAGCAAACTGGT 4 GTTGTCGCCCTTTTCTACTTTGCCAGCA 24 human_412
AACTGGTGCTCAAGGCC 5 BAX_NM_004324_ GGTTGGGTGAGACTCCTCAA 5
ATCCAAGACCAGGGTGGTTGGGTGAG 25 human_538 ACTCCTCAAGCCTCCTCAC 6
BAX_NM_004324_ CTACTTTGCCAGCAAACTGG 6 GGTTGTCGCCCTTTTCTACTTTGCCAGC
26 human_411 AAACTGGTGCTCAAGGC 7 BAX_NM_004324_
GCGTTTTCCTTACGTGTCTG 7 GATGTGGTCTATAATGCGTTTTCCTTA 27 human_706
CGTGTCTGATCAATCCCC 8 BAX_NM_004324_ TACGTGTCTGATCAATCCCC 8
ATAATGCGTTTTCCTTACGTGTCTGATC 28 human_7 16 AATCCCCGATTCATCTA 9
BAX_NM_004324_ TCAGGGTTTCATCCAGGATC 9 AGGGGCCCTTTTGCTTCAGGGTTTCAT
29 human_ 50 CCAGGATCGAGCAGGGCG 10 BAX_NM_004324_
TGACGGCAACTTCAACTGGG 10 AGCTGACATGTTTTCTGACGGCAACTT 30 human_ 72
CAACTGGGGCCGGGTTGT 11 BAX_NM_004324_ CAGCTGACATGTTTTCTGAC 11
TCTTTTTCCGAGTGGCAGCTGACATGT 31 human_356 TTTCTGACGGCAACTTCA 12
BAX_NM_004324_ AGCTGACATGTTTTCTGACG 12 CTTTTTCCGAGTGGCAGCTGACATGTT
32 human_357 TTCTGACGGCAACTTCAA 13 BAX_NM_004324_
CACTGTGACCTTGACTTGAT 13 AGTGACCCCTGACCTCACTGTGACCTT 33 human_776
GACTTGATTAGTGCCTTC 14 BAX_NM_004324_ TCCTTACGTGTCTGATCAAT 14
GTCTATAATGCGTTTTCCTTACGTGTCT 34 human_712 GATCAATCCCCGATTCA 15
BAX_NM_004324_ GATCAGAACCATCATGGGCT 15 CAAGGTGCCGGAACTGATCAGAACCA
35 human_465 TCATGGGCTGGACATTGGA 16 BAX_NM_004324_
CTTCTGGAGCAGGTCACAGT 16 TCTGGGACCCTGGGCCTTCTGGAGCA 36 human_642
GGTCACAGTGGTGCCCTCT 17 BAX_NM_004324_ TGAGCAGATCATGAAGACAG 17
GGGGCCCACCAGCTCTGAGCAGATCA 37 human_117 TGAAGACAGGGGCCCTTTT 18
BAX_NM_004324_ TATAATGCGTTTTCCTTACG 18 TCATCAGATGTGGTCTATAATGCGTTT
38 human_700 TCCTTACGTGTCTGATCA 19 BAX_NM_004324_
CCCATCTTCAGATCATCAGA 19 CAGTGGTGCCCTCTCCCCATCTTCAGA 39 human_673
TCATCAGATGTGGTCTAT 20 BAX_NM_004324_ AGGTGCCGGAACTGATCAGA 20
AGGCCCTGTGCACCAAGGTGCCGGAA 40 human_452 CTGATCAGAACCATCATGG
Accession: NM_001188 HUGO gene symbol: BAK1 1 BAK1_NM_001188
TGGTTTGTTATATCAGGGAA 41 ACAGGGCTTAGGACTTGGTTTGTTA 61 _human_1813
TATCAGGGAAAAGGAGTAGG 2 BAK1_NM_001188 TGGTACGAAGATTCTTCAAA 42
TGTTGGGCCAGTTTGTGGTACGAAG 62 _human_911 ATTCTTCAAATCATGACTCC 3
BAK1_NM_001188 TTATATCAGGGAAAAGGAGT 43 TTAGGACTTGGTTTGTTATATCAGG 63
_human_1820 GAAAAGGAGTAGGGAGTTCA 4 BAK1_NM_001188
TCCCTTCCTCTCTCCTTATA 44 GTCCTCTCAGTTCTCTCCCTTCCTCTC 64 _human_1678
TCCTTATAGACACTTGCT 5 BAK1_NM_001188 TCAAATCATGACTCCCAAGG 45
TGGTACGAAGATTCTTCAAATCATG 65 _human_926 ACTCCCAAGGGTGCCCTTTG 6
BAK1_NM_001188 TGTTATATCAGGGAAAAGGA 46 GCTTAGGACTTGGTTTGTTATATCA 66
_human_1818 GGGAAAAGGAGTAGGGAGTT 7 BAK1_NM_001188
ACGAAGATTCTTCAAATCAT 47 GGGCCAGTTTGTGGTACGAAGATTC 67 _human_915
TTCAAATCATGACTCCCAAG 8 BAK1_NM_001188 GGTACGAAGATTCTTCAAAT 48
GTTGGGCCAGTTTGTGGTACGAAGA 68 _human_912 TTCTTCAAATCATGACTCCC 9
BAK1_NM_001188 GAAGTTCTTGATTCAGCCAA 49 GGGGGTCAGGGGGGAGAAGTTCTT 69
_human_2086 GATTCAGCCAAATGCAGGGAG 10 BAK1_NM_001188
CCTATGAGTACTTCACCAAG 50 CCACGGCAGAGAATGCCTATGAGTA 70 _human_620
CTTCACCAAGATTGCCACCA 11 BAK1_NM_001188 TATCAGGGAAAAGGAGTAGG 51
GGACTTGGTTTGTTATATCAGGGAA 71 _human_1823 AAGGAGTAGGGAGTTCATCT 12
BAK1_NM_001188 CTCTCCTTATAGACACTTGC 52 GTTCTCTCCCTTCCTCTCTCCTTATAG
72 _human_1687 ACACTTGCTCCCAACCCA 13 BAK1_NM_001188
ACTTGGTTTGTTATATCAGG 53 ACTACAGGGCTTAGGACTTGGTTTG 73 _human_1810
TTATATCAGGGAAAAGGAGT 14 BAK1_NM_001188 AAGATCAGCACCCTAAGAGA 54
ATTCAGCTATTCTGGAAGATCAGCA 74 _human_1399 CCCTAAGAGATGGGACTAGG 15
BAK1_NM_001188 GTTTGAGAGTGGCATCAATT 55 GATTGCCACCAGCCTGTTTGAGAGT 75
_human_654 GGCATCAATTGGGGCCGTGT 16 BAK1_NM_001188
GACTATCAACACCACTAGGA 56 TCTAAGTGGGAGAAGGACTATCAAC 76 _human_1875
ACCACTAGGAATCCCAGAGG 17 BAK1_NM_001188 AGCTTTAGCAAGTGTGCACT 57
CCTCAAGAGTACAGAAGCTTTAGCA 77 _human_1043 AGTGTGCACTCCAGCTTCGG 18
BAK1_NM_001188 TTCATCTGGAGGGTTCTAAG 58 AAAAGGAGTAGGGAGTTCATCTGG 78
_human_1846 AGGGTTCTAAGTGGGAGAAGG 19 BAK1_NM_001188
AAGTTCTTGATTCAGCCAAA 59 GGGGTCAGGGGGGAGAAGTTCTTG 79 _human_2087
ATTCAGCCAAATGCAGGGAGG 20 BAK1_NM_001188 GTTATATCAGGGAAAAGGAG 60
CTTAGGACTTGGTTTGTTATATCAG 80 _human_1819 GGAAAAGGAGTAGGGAGTTC
Accession: NM_001228 HUGO gene symbol: CASP8 1 CASP8_NM_001228
TTAAATCATTAGGAATTAAG 121 TCTGCTTGGATTATTTTAAATCATTAG 141
_human_2821 GAATTAAGTTATCTTTAA 2 CASP8_NM_001228
GAATTAAGTTATCTTTAAAA 122 ATTTTAAATCATTAGGAATTAAGTTAT 142
_human_2833 CTTTAAAATTTAAGTATC 3 CASP8_NM_001228
AACTTTAATTCTCTTTCAAA 123 TGTTAATATTCTATTAACTTTAATTCT 143
_human_2392 CTTTCAAAGCTAAATTCC 4 CASP8_NM_001228
GACTGAAGTGAACTATGAAG 124 TATTCTCACCATCCTGACTGAAGTGA 144 _human_1683
ACTATGAAGTAAGCAACAA 5 CASP8_NM_001228 ATATTCTCCTGCCTTTTAAA 125
GGGAATATTGAGATTATATTCTCCTG 145 _human_281 CCTTTTAAAAAGATGGACT 6
CASP8_NM_001228 AGTTATCTTTAAAATTTAAG 126 AATCATTAGGAATTAAGTTATCTTTA
146 _human_2839 AAATTTAAGTATCTTTTTT 7 CASP8_NM_001228
TAGATTTTCTACTTTATTAA 127 TATTTACTAATTTTCTAGATTTTCTACT 147
_human_2164 TTATTAATTGTTTTGCA 8 CASP8_NM_001228
CTGTGCCCAAATCAACAAGA 128 CATCCTGAAAAGAGTCTGTGCCCAAA 148 _human_888
TCAACAAGAGCCTGCTGAA 9 CASP8_NM_001228 AGCTGGTGGCAATAAATACC 129
TTTGGGAATGTTTTTAGCTGGTGGCA 149 _human_2283 ATAAATACCAGACACGTAC 10
CASP8_NM_001228 TCCTACCGAAACCCTGCAGA 130 GTGAATAACTGTGTTTCCTACCGAAA
150 _human_1585 CCCTGCAGAGGGAACCTGG 11 CASP8_NM_001228
TATAAGAGCTAAAGTTAAAT 131 TGTTTTGCACTTTTTTATAAGAGCTAA 151
_human_2200 AGTTAAATAGGATATTAA 12 CASP8_NM_001228
CACTATGTTTATTTACTAAT 132 ACTATTTAGATATAACACTATGTTTAT 152
_human_2140 TTACTAATTTTCTAGATT 13 CASP8_NM_001228
ATTGTTATCTATCAACTATA 133 GGGCTTATGATTCAGATTGTTATCTA 153 _human_2350
TCAACTATAAGCCCACTGT 14 CASP8_NM_001228 TAACTGTGTTTCCTACCGAA 134
GATGGCCACTGTGAATAACTGTGTTT 154 _human_1575 CCTACCGAAACCCTGCAGA 15
CASP8_NM_001228 TAATTCTCTTTCAAAGCTAA 135
ATATTCTATTAACTTTAATTCTCTTTCA 155 _human_2397 AAGCTAAATTCCACACT 16
CASP8_NM_001228 TATATGCTTGGCTAACTATA 136
TGCTTTTATGATATATATATGCTTGGC 156 _human_2726 TAACTATATTTGCTTTTT 17
CASP8_NM_001228 CTCTGCTTGGATTATTTTAA 137
CATTTGCTCTTTCATCTCTGCTTGGAT 157 _human_2805 TATTTTAAATCATTAGGA 18
CASP8_NM_001228 ATGCTTGGCTAACTATATTT 138
TTTTATGATATATATATGCTTGGCTAA 158 _human_2729 CTATATTTGCTTTTTGCT 19
CASP8_NM_001228 ATAAGAGCTAAAGTTAAATA 139
GTTTTGCACTTTTTTATAAGAGCTAAA 159 _human_2201 GTTAAATAGGATATTAAC 20
CASP8_NM_001228 ATCTTTAAAATTTAAGTATC 140
ATTAGGAATTAAGTTATCTTTAAAATT 160 _human_2843 TAAGTATCTTTTTTCAAA
Accession: NM_000675 HUGO gene symbol: ADORA2A 1 ADORA2A_NM_00067
TAACTGCCTTTCCTTCTAAA 161 GTGAGAGGCCTTGTCTAACTGCC 181 5_human_2482
TTTCCTTCTAAAGGGAATGTTT 2 ADORA2A_NM_00067 TTCCTTCTAAAGGGAATGTT 162
CTTGTCTAACTGCCTTTCCTTCTAA 182 5_human_2491 AGGGAATGTTTTTTTCTGAG 3
ADORA2A_NM_00067 GCCTTTCCTTCTAAAGGGAA 163 AGGCCTTGTCTAACTGCCTTTCCT
183 5_human_2487 TCTAAAGGGAATGTTTTTTTC 4 ADORA2A_NM_00067
TTTTCTGAGATAAAATAAAA 164 CTAAAGGGAATGTTTTTTTCTGAG 184 5_human_2512
ATAAAATAAAAACGAGCCACA 5 ADORA2A_NM_00067 CATCTCTTGGAGTGACAAAG 165
TCTCAGTCCCAGGGCCATCTCTTG 185 5_human_2330 GAGTGACAAAGCTGGGATCAA 6
ADORA2A_NM_00067 CATGGTGTACTTCAACTTCT 166 GGTCCCCATGAACTACATGGTGT
186 5_human_987 ACTTCAACTTCTTTGCCTGTGT 7 ADORA2A_NM_00067
CTAACTGCCTTTCCTTCTAA 167 AGTGAGAGGCCTTGTCTAACTGC 187 5_human_2481
CTTTCCTTCTAAAGGGAATGTT 8 ADORA2A_NM_00067 CTGATGATTCATGGAGTTTG 168
TGGAGCAGGAGTGTCCTGATGAT 188 5_human_1695 TCATGGAGTTTGCCCCTTCCTA 9
ADORA2A_NM_00067 CTCAGAGTCCTCTGTGAAAA 169 CCTGGTTTCAGGAGACTCAGAGT
189 5_human_264 CCTCTGTGAAAAAGCCCTTGGA 10 ADORA2A_NM_00067
AACGAGCCACATCGTGTTTT 170 CTGAGATAAAATAAAAACGAGCC 190 5_human_2531
ACATCGTGTTTTAAGCTTGTCC 11 ADORA2A_NM_00067 TCCTTCTAAAGGGAATGTTT 171
TTGTCTAACTGCCTTTCCTTCTAAA 191 5_human_2492 GGGAATGTTTTTTTCTGAGA 12
ADORA2A_NM_00067 CATGAACTACATGGTGTACT 172 TGAGGATGTGGTCCCCATGAACT
192 5_human_978 ACATGGTGTACTTCAACTTCTT 13 ADORA2A_NM_00067
AACTGCCTTTCCTTCTAAAG 173 TGAGAGGCCTTGTCTAACTGCCTT 193 5_human_2483
TCCTTCTAAAGGGAATGTTTT
14 ADORA2A_NM_00067 CAGATGTTTCATGCTGTGAG 174
TGGGTTCTGAGGAAGCAGATGTT 194 5_human_1894 TCATGCTGTGAGGCCTTGCACC 15
ADORA2A_NM_00067 CCCATGAACTACATGGTGTA 175 TTTGAGGATGTGGTCCCCATGAA
195 5_human_976 CTACATGGTGTACTTCAACTTC 16 ADORA2A_NM_00067
AGGCAGCAAGAACCTTTCAA 176 CGCAGCCACGTCCTGAGGCAGCA 196 5_human_1384
AGAACCTTTCAAGGCAGCTGGC 17 ADORA2A_NM_00067 GTCCTGATGATTCATGGAGT 177
GGATGGAGCAGGAGTGTCCTGAT 197 5_human_1692 GATTCATGGAGTTTGCCCCTTC 18
ADORA2A_NM_00067 GTACTTCAACTTCTTTGCCT 178 CATGAACTACATGGTGTACTTCAA
198 5_human_993 CTTCTTTGCCTGTGTGCTGGT 19 ADORA2A_NM_00067
TGTAAGTGTGAGGAAACCCT 179 TTTTTCCAGGAAAAATGTAAGTGT 199 5_human_2167
GAGGAAACCCTTTTTATTTTA 20 ADORA2A_NM_00067 CCTACTTTGGACTGAGAGAA 180
TGAGGGCAGCCGGTTCCTACTTT 200 5_human_1815 GGACTGAGAGAAGGGAGCCCCA
Accession: NM_005214 HUGO gene symbol: CTLA4 1 CTLA4_NM_005214_
TGATTCTGTGTGGGTTCAAA 201 TCTATATAAAGTCCTTGATTCTGT 221 human_61
GTGGGTTCAAACACATTTCAA 2 CTLA4_NM_005214_ TTATTTGTTTGTGCATTTGG 202
GCTATCCAGCTATTTTTATTTGTTT 222 human_909 GTGCATTTGGGGGGAATTCA 3
CTLA4_NM_005214_ TGATTACATCAAGGCTTCAA 203 TCTTAAACAAATGTATGATTACAT
223 human_1265 CAAGGCTTCAAAAATACTCAC 4 CTLA4_NM_005214_
GATGTGGGTCAAGGAATTAA 204 GGGATGCAGCATTATGATGTGGG 224 human_1094
TCAAGGAATTAAGTTAGGGAAT 5 CTLA4_NM_005214_ CCTTTTATTTCTTAAACAAA 205
AAGTTAAATTTTATGCCTTTTATTT 225 human_1241 CTTAAACAAATGTATGATTA 6
CTLA4_NM_005214_ GATTACATCAAGGCTTCAAA 206 CTTAAACAAATGTATGATTACATC
226 human_1266 AAGGCTTCAAAAATACTCACA 7 CTLA4_NM_005214_
TCTGTGTGGGTTCAAACACA 207 TATAAAGTCCTTGATTCTGTGTGG 227 human_65
GTTCAAACACATTTCAAAGCT 8 CTLA4_NM_005214_ TTGATAGTATTGTGCATAGA 208
TATATATATTTTAATTTGATAGTAT 228 human_1405 TGTGCATAGAGCCACGTATG 9
CTLA4_NM_005214_ TGCCTTTTATTTCTTAAACA 209 TCAAGTTAAATTTTATGCCTTTTAT
229 human_1239 TTCTTAAACAAATGTATGAT 10 CTLA4_NM_005214_
TCCATGAAAATGCAACAACA 210 TTTAACTCAATATTTTCCATGAAA 230 human_1912
ATGCAACAACATGTATAATAT 11 CTLA4_NM_005214_ TTATTTCTTAAACAAATGTA 211
TAAATTTTATGCCTTTTATTTCTTA 231 human_1245 AACAAATGTATGATTACATC 12
CTLA4_NM_005214_ TTAATGGTTTGAATATAAAC 212 GTTTTTGTGTATTTGTTAATGGTTT
232 human_1449 GAATATAAACACTATATGGC 13 CTLA4_NM_005214_
ATGTGGGTCAAGGAATTAAG 213 GGATGCAGCATTATGATGTGGGT 233 human_1095
CAAGGAATTAAGTTAGGGAATG 14 CTLA4_NM_005214_ AGCCGAAATGATCTTTTCAA 214
GTATGAGACGTTTATAGCCGAAA 234 human_1208 TGATCTTTTCAAGTTAAATTTT 15
CTLA4_NM_005214_ GTTTGAATATAAACACTATA 215 GTGTATTTGTTAATGGTTTGAATA
235 human_1455 TAAACACTATATGGCAGTGTC 16 CTLA4_NM_005214_
TATGCCTTTTATTTCTTAAA 216 TTTCAAGTTAAATTTTATGCCTTTT 236 human_1237
ATTTCTTAAACAAATGTATG 17 CTLA4_NM_005214_ TTCCATGAAAATGCAACAAC 217
TTTTAACTCAATATTTTCCATGAA 237 human_1911 AATGCAACAACATGTATAATA 18
CTLA4_NM_005214_ CATCTCTCTTTAATATAAAG 218 CATTTGGGGGGAATTCATCTCTCT
238 human_937 TTAATATAAAGTTGGATGCGG 19 CTLA4_NM_005214_
GGAATTCATCTCTCTTTAAT 219 TTTGTGCATTTGGGGGGAATTCAT 239 human_931
CTCTCTTTAATATAAAGTTGG 20 CTLA4_NM_005214_ ATCTATATAAAGTCCTTGAT 220
TCTGGGATCAAAGCTATCTATATA 240 human_45 AAGTCCTTGATTCTGTGTGGG
Accession: NM_002286 HUGO gene symbol: LAG3 1 LAG3_NM_002286
GACTTTACCCTTCGACTAGA 241 ACTGGAGACAATGGCGACTTTACC 261 _human_1292
CTTCGACTAGAGGATGTGAGC 2 LAG3_NM_002286 CAACGTCTCCATCATGTATA 242
CTACAGAGATGGCTTCAACGTCTC 262 _human_1096 CATCATGTATAACCTCACTGT 3
LAG3_NM_002286 GTCCTTTCTCTGCTCCTTTT 243 TTTCTCATCCTTGGTGTCCTTTCTCT
263 _human_1721 GCTCCTTTTGGTGACTGGA 4 LAG3_NM_002286
TCCAGTATCTGGACAAGAAC 244 GCTTTGTGAGGTGACTCCAGTATC 264 _human_1465
TGGACAAGAACGCTTTGTGTG 5 LAG3_NM_002286 ATTTTCTGCCTTAGAGCAAG 245
GTGGCGACCAAGACGATTTTCTGC 265 _human_1795 CTTAGAGCAAGGGATTCACCC 6
LAG3_NM_002286 TTTCACCTTTGGAGAAGACA 246 ACTGGAGCCTTTGGCTTTCACCTTT
266 _human_1760 GGAGAAGACAGTGGCGACCA 7 LAG3_NM_002286
CATTTTGAACTGCTCCTTCA 247 AGCCTCCGACTGGGTCATTTTGAA 267 _human_904
CTGCTCCTTCAGCCGCCCTGA 8 LAG3_NM_002286 TCATCACAGTGACTCCCAAA 248
CTGTCACATTGGCAATCATCACAGT 268 _human_1398 GACTCCCAAATCCTTTGGGT 9
LAG3_NM_002286 GCTTTCACCTTTGGAGAAGA 249 TGACTGGAGCCTTTGGCTTTCACCT
269 _human_1758 TTGGAGAAGACAGTGGCGAC 10 LAG3_NM_002286
CTTTGGCTTTCACCTTTGGA 250 TTTGGTGACTGGAGCCTTTGGCTTT 270 _human_1753
CACCTTTGGAGAAGACAGTG 11 LAG3_NM_002286 ATTTTGAACTGCTCCTTCAG 251
GCCTCCGACTGGGTCATTTTGAACT 271 _human_905 GCTCCTTCAGCCGCCCTGAC 12
LAG3_NM_002286 CACATTGGCAATCATCACAG 252 GCTCAATGCCACTGTCACATTGGC
272 _human_1387 AATCATCACAGTGACTCCCAA 13 LAG3_NM_002286
TTTCTGACCTCCTTTTGGAG 253 ACTGCCCCCTTTCCTTTTCTGACCTC 273 _human_301
CTTTTGGAGGGCTCAGCGC 14 LAG3_NM_002286 CGACTGGGTCATTTTGAACT 254
ATCTCTCAGAGCCTCCGACTGGGT 274 _human_895 CATTTTGAACTGCTCCTTCAG 15
LAG3_NM_002286 TACTTCACAGAGCTGTCTAG 255 CTTGGAGCAGCAGTGTACTTCACA
275 _human_1625 GAGCTGTCTAGCCCAGGTGCC 16 LAG3_NM_002286
ATTGGCAATCATCACAGTGA 256 CAATGCCACTGTCACATTGGCAATC 276 _human_1390
ATCACAGTGACTCCCAAATC 17 LAG3_NM_002286 CTGTTTCTCATCCTTGGTGT 257
GCAGGCCACCTCCTGCTGTTTCTCA 277 _human_1703 TCCTTGGTGTCCTTTCTCTG 18
LAG3_NM_002286 TTGTGAGGTGACTCCAGTAT 258 CCTGGGGAAGCTGCTTTGTGAGGT
278 _human_1453 GACTCCAGTATCTGGACAAGA 19 LAG3_NM_002286
TTTGGCTTTCACCTTTGGAG 259 TTGGTGACTGGAGCCTTTGGCTTTC 279 _human_1754
ACCTTTGGAGAAGACAGTGG 20 LAG3_NM_002286 TGGAGACAATGGCGACTTTA 260
TGACCTCCTGGTGACTGGAGACAA 280 _human_1279 TGGCGACTTTACCCTTCGACT
Accession: NM_005018 HUGO gene symbol: PDCD1 1 PDCD1_NM_005018
TATTATATTATAATTATAAT 281 CCTTCCCTGTGGTTCTATTATATTAT 301 _human_2070
AATTATAATTAAATATGAG 2 PDCD1_NM_005018 TCTATTATATTATAATTATA 282
CCCCTTCCCTGTGGTTCTATTATATT 302 _human_2068 ATAATTATAATTAAATATG 3
PDCD1_NM_005018 CATTCCTGAAATTATTTAAA 283 GCTCTCCTTGGAACCCATTCCTGAA
303 _human_1854 ATTATTTAAAGGGGTTGGCC 4 PDCD1_NM_005018
CTATTATATTATAATTATAA 284 CCCTTCCCTGTGGTTCTATTATATT 304 _human_2069
ATAATTATAATTAAATATGA 5 PDCD1_NM_005018 AGTTTCAGGGAAGGTCAGAA 285
CTGCAGGCCTAGAGAAGTTTCAGG 305 _human_1491 GAAGGTCAGAAGAGCTCCTGG 6
PDCD1_NM_005018 TGTGGTTCTATTATATTATA 286 GGGATCCCCCTTCCCTGTGGTTCTA
306 _human_2062 TTATATTATAATTATAATTA 7 PDCD1_NM_005018
TGTGTTCTCTGTGGACTATG 287 CCCCTCAGCCGTGCCTGTGTTCTCT 307 _human_719
GTGGACTATGGGGAGCTGGA 8 PDCD1_NM_005018 CCCATTCCTGAAATTATTTA 288
GAGCTCTCCTTGGAACCCATTCCTG 308 _human_1852 AAATTATTTAAAGGGGTTGG 9
PDCD1_NM_005018 TGCCACCATTGTCTTTCCTA 289 TGAGCAGACGGAGTATGCCACCAT
309 _human_812 TGTCTTTCCTAGCGGAATGGG 10 PDCD1_NM_005018
AAGTTTCAGGGAAGGTCAGA 290 CCTGCAGGCCTAGAGAAGTTTCAG 310 _human_1490
GGAAGGTCAGAAGAGCTCCTG 11 PDCD1_NM_005018 CTGTGGTTCTATTATATTAT 291
AGGGATCCCCCTTCCCTGTGGTTCT 311 _human_2061 ATTATATTATAATTATAATT 12
PDCD1_NM_005018 TTCTATTATATTATAATTAT 292 CCCCCTTCCCTGTGGTTCTATTATA
312 _human_2067 TTATAATTATAATTAAATAT 13 PDCD1_NM_005018
TTTCAGGGAAGGTCAGAAGA 293 GCAGGCCTAGAGAAGTTTCAGGG 313 _human_1493
AAGGTCAGAAGAGCTCCTGGCT 14 PDCD1_NM_005018 CTTGGAACCCATTCCTGAAA 294
ACCCTGGGAGCTCTCCTTGGAACC 314 _human_1845 CATTCCTGAAATTATTTAAAG 15
PDCD1_NM_005018 TCCCTGTGGTTCTATTATAT 295 ACAAGGGATCCCCCTTCCCTGTGG
315 _human_2058 TTCTATTATATTATAATTATA 16 PDCD1_NM_005018
CCTGTGGTTCTATTATATTA 296 AAGGGATCCCCCTTCCCTGTGGTTC 316 _human_2060
TATTATATTATAATTATAAT 17 PDCD1_NM_005018 TGGAACCCATTCCTGAAATT 297
CCTGGGAGCTCTCCTTGGAACCCA 317 _human_1847 TTCCTGAAATTATTTAAAGGG 18
PDCD1_NM_005018 CCTTCCCTGTGGTTCTATTA 298 GGGACAAGGGATCCCCCTTCCCTG
318 _human_2055 TGGTTCTATTATATTATAATT 19 PDCD1_NM_005018
TTCCCTGTGGTTCTATTATA 299 GACAAGGGATCCCCCTTCCCTGTG 319 _human_2057
GTTCTATTATATTATAATTAT 20 PDCD1_NM_005018 CACAGGACTCATGTCTCAAT 300
CAGGCACAGCCCCACCACAGGACT 320 _human_1105 CATGTCTCAATGCCCACAGTG
Accession: NM_004612 HUGO gene symbol: TGFBR1 1 TGFBR1_NM_004612
CCTGTTTATTACAACTTAAA 321 GTTAATAACATTCAACCTGTTTAT 341 _human_5263
TACAACTTAAAAGGAACTTCA 2 TGFBR1_NM_004612 CCATTGGTGGAATTCATGAA 322
TTGCTCGACGATGTTCCATTGGTG 342 _human_1323 GAATTCATGAAGATTACCAAC 3
TGFBR1_NM_004612 TTTTCCTTATAACAAAGACA 323 TTTAGGGATTTTTTTTTTTCCTTAT
343 _human_6389 AACAAAGACATCACCAGGAT 4 TGFBR1_NM_004612
TGTATTACTTGTTTAATAAT 324 TTTTTATAGTTGTGTTGTATTACTT 344 _human_3611
GTTTAATAATAATCTCTAAT 5 TGFBR1_NM_004612 TTATTGAATCAAAGATTGAG 325
TGCTGAAGATATTTTTTATTGAAT 345 _human_3882 CAAAGATTGAGTTACAATTAT 6
TGFBR1_NM_004612 TTCTTACCTAAGTGGATAAA 326 GTTACAATTATACTTTTCTTACCTA
346 _human_3916 AGTGGATAAAATGTACTTTT 7 TGFBR1_NM_004612
ATGTTGCTCAGTTACTCAAA 327 TAAAGTATGGGTATTATGTTGCTC 347 _human_5559
AGTTACTCAAATGGTACTGTA 8 TGFBR1_NM_004612 ATATTTGTACCCCAAATAAC 328
GGTACTGTATTGTTTATATTTGTA 348 _human_5595 CCCCAAATAACATCGTCTGTA 9
TGFBR1_NM_004612 TGTAAATGTAAACTTCTAAA 329 TTATGCAATCTTGTTTGTAAATGT
349 _human_5222 AAACTTCTAAAAATATGGTTA 10 TGFBR1_NM_004612
AGAATGAGTGACATATTACA 330 AACCAAAGTAATTTTAGAATGAG 350 _human_3435
TGACATATTACATAGGAATTTA 11 TGFBR1_NM_004612 CCATTTCTAAGCCTACCAGA 331
GTTGTTGTTTTTGGGCCATTTCTA 351 _human_3709 AGCCTACCAGATCTGCTTTAT 12
TGFBR1_NM_004612 ATATTCCAAAAGAATGTAAA 332 ATTGTATTTGTAGTAATATTCCAA
352 _human_5826 AAGAATGTAAATAGGAAATAG 13 TGFBR1_NM_004612
TTACTTCCAATGCTATGAAG 333 TATAATAACTGGTTTTTACTTCCA 353 _human_3146
ATGCTATGAAGTCTCTGCAGG
14 TGFBR1_NM_004612 TCTTTATCTGTTCAAAGACT 334
TGTAAGCCATTTTTTTCTTTATCTG 354 _human_2675 TTCAAAGACTTATTTTTTAA 15
TGFBR1_NM_004612 GTCTAAGTATACTTTTAAAA 335 CATTTTAATTGTGTTGTCTAAGTA
355 _human_2529 TACTTTTAAAAAATCAAGTGG 16 TGFBR1_NM_004612
ATCTTTGGACATGTACTGCA 336 GAGATACTAAGGATTATCTTTGG 356 _human_5079
ACATGTACTGCAGCTTCTTGTC 17 TGFBR1_NM_004612 GTGTTGTATTACTTGTTTAA 337
TTTGTTTTTATAGTTGTGTTGTATT 357 _human_3607 ACTTGTTTAATAATAATCTC 18
TGFBR1_NM_004612 TGCTGTAGATGGCAACTAGA 338 CATGCCATATGTAGTTGCTGTAGA
358 _human_5994 TGGCAACTAGAACCTTTGAGT 19 TGFBR1_NM_004612
TCTTTCACTTATTCAGAACA 339 GTATACTATTATTGTTCTTTCACTT 359 _human_2177
ATTCAGAACATTACATGCCT 20 TGFBR1_NM_004612 GTATTTGTAGTAATATTCCA 340
TTTAAATTGTATATTGTATTTGTA 360 _human_5814 GTAATATTCCAAAAGAATGTA
Accession: NM_032782 HUGO gene symbol: HAVCR2 1 HAVCR2_NM_032782
CTCATAGCAAAGAGAAGATA 361 TTTTCAAATGGTATTCTCATAGCA 381 _human_937
AAGAGAAGATACAGAATTTAA 2 HAVCR2_NM_032782 GTATTCTCATAGCAAAGAGA 362
TTTAATTTTCAAATGGTATTCTCAT 382 _human_932 AGCAAAGAGAAGATACAGAA 3
HAVCR2_NM_032782 TTGCTTGTTGTGTGCTTGAA 363 TGTATTGGCCAAGTTTTGCTTGTT
383 _human_2126 GTGTGCTTGAAAGAAAATATC 4 HAVCR2_NM_032782
TATTCGTGGACCAAACTGAA 364 TCTGACCAACTTCTGTATTCGTGG 384 _human_2171
ACCAAACTGAAGCTATATTTT 5 HAVCR2_NM_032782 ATTGTGGAGTAGACAGTTGG 365
GCTACTGCTCATGTGATTGTGGA 385 _human_158 GTAGACAGTTGGAAGAAGTACC 6
HAVCR2_NM_032782 GTTGTGTGCTTGAAAGAAAA 366 GGCCAAGTTTTGCTTGTTGTGTGC
386 _human_2132 TTGAAAGAAAATATCTCTGAC 7 HAVCR2_NM_032782
TGTTGTGTGCTTGAAAGAAA 367 TGGCCAAGTTTTGCTTGTTGTGTG 387 _human_2131
CTTGAAAGAAAATATCTCTGA 8 HAVCR2_NM_032782 CCCTAAACTTAAATTTCAAG 368
TTGACAGAGAGTGGTCCCTAAAC 388 _human_2313 TTAAATTTCAAGACGGTATAGG 9
HAVCR2_NM_032782 ACATCCAGATACTGGCTAAA 369 GATGTGAATTATTGGACATCCAG
389 _human_489 ATACTGGCTAAATGGGGATTTC 10 HAVCR2_NM_032782
CATTTTCAGAAGATAATGAC 370 GGAGCAGAGTTTTCCCATTTTCAG 390 _human_1272
AAGATAATGACTCACATGGGA 11 HAVCR2_NM_032782 CACATTGGCCAATGAGTTAC 371
TCTAACACAAATATCCACATTGGC 391 _human_785 CAATGAGTTACGGGACTCTAG 12
HAVCR2_NM_032782 TGCTTGTTGTGTGCTTGAAA 372 GTATTGGCCAAGTTTTGCTTGTTG
392 _human_2127 TGTGCTTGAAAGAAAATATCT 13 HAVCR2_NM_032782
GAGTAGACAGTTGGAAGAAG 373 GCTCATGTGATTGTGGAGTAGAC 393 _human_164
AGTTGGAAGAAGTACCCAGTCC 14 HAVCR2_NM_032782 TTGTTGTGTGCTTGAAAGAA 374
TTGGCCAAGTTTTGCTTGTTGTGT 394 _human_2130 GCTTGAAAGAAAATATCTCTG 15
HAVCR2_NM_032782 CGGCGCTTTAATTTTCAAAT 375 TCTGGCTCTTATCTTCGGCGCTTT
395 _human_911 AATTTTCAAATGGTATTCTCA 16 HAVCR2_NM_032782
TTTGGCACAGAAAGTCTAAA 376 TGAAAGCATAACTTTTTTGGCACA 396 _human_1543
GAAAGTCTAAAGGGGCCACTG 17 HAVCR2_NM_032782 GATCTGTCTTGCTTATTGTT 377
AGACGGTATAGGCTTGATCTGTC 397 _human_2346 TTGCTTATTGTTGCCCCCTGCG 18
HAVCR2_NM_032782 GGTGTGTATTGGCCAAGTTT 378 GAAGTGCATTTGATTGGTGTGTA
398 _human_2107 TTGGCCAAGTTTTGCTTGTTGT 19 HAVCR2_NM_032782
CCCATTTTCAGAAGATAATG 379 ATGGAGCAGAGTTTTCCCATTTTC 399 _human_1270
AGAAGATAATGACTCACATGG 20 HAVCR2_NM_032782 TGGCACAGAAAGTCTAAAGG 380
AAAGCATAACTTTTTTGGCACAGA 400 _human_1545 AAGTCTAAAGGGGCCACTGAT
Accession: NM_002987 HUGO gene symbol: CCL17 1 CCL17_NM_002987
AAATACCTGCAAAGCCTTGA 401 GTGAAGAATGCAGTTAAATACCTGC 421 _human_385
AAAGCCTTGAGAGGTCTTGA 2 CCL17_NM_002987 TTTTGTAACTGTGCAGGGCA 402
CAGGGATGCCATCGTTTTTGTAACT 422 _human_318 GTGCAGGGCAGGGCCATCTG 3
CCL17_NM_002987 AGAGTGAAGAATGCAGTTAA 403 GACCCCAACAACAAGAGAGTGAAG
423 _human_367 AATGCAGTTAAATACCTGCAA 4 CCL17_NM_002987
AAGCCTTGAGAGGTCTTGAA 404 AGTTAAATACCTGCAAAGCCTTGAG 424 _human_396
AGGTCTTGAAGCCTCCTCAC 5 CCL17_NM_002987 AATACCTGCAAAGCCTTGAG 405
TGAAGAATGCAGTTAAATACCTGCA 425 _human_386 AAGCCTTGAGAGGTCTTGAA 6
CCL17_NM_002987 TGCAGTTAAATACCTGCAAA 406 CAAGAGAGTGAAGAATGCAGTTAA
426 _human_378 ATACCTGCAAAGCCTTGAGAG 7 CCL17_NM_002987
CAACAACAAGAGAGTGAAGA 407 CATCTGTTCGGACCCCAACAACAAG 427 _human_357
AGAGTGAAGAATGCAGTTAA 8 CCL17_NM_002987 CTGAATTCAAAACCAGGGTG 408
CTGCTGATGGGAGAGCTGAATTCAA 428 _human_55 AACCAGGGTGTCTCCCTGAG 9
CCL17_NM_002987 ATACCTGCAAAGCCTTGAGA 409 GAAGAATGCAGTTAAATACCTGCAA
429 _human_387 AGCCTTGAGAGGTCTTGAAG 10 CCL17_NM_002987
TTCCCCTTAGAAAGCTGAAG 410 ACTTCAAGGGAGCCATTCCCCTTAG 430 _human_254
AAAGCTGAAGACGTGGTACC 11 CCL17_NM_002987 GGAGAGCTGAATTCAAAACC 411
CACCGCCTGCTGATGGGAGAGCTG 431 _human_49 AATTCAAAACCAGGGTGTCTC 12
CCL17_NM_002987 GCAGTTAAATACCTGCAAAG 412 AAGAGAGTGAAGAATGCAGTTAAA
432 _human_379 TACCTGCAAAGCCTTGAGAGG 13 CCL17_NM_002987
GAAGAATGCAGTTAAATACC 413 CAACAACAAGAGAGTGAAGAATGC 433 _human_372
AGTTAAATACCTGCAAAGCCT 14 CCL17_NM_002987 ATGCAGTTAAATACCTGCAA 414
ACAAGAGAGTGAAGAATGCAGTTA 434 _human_377 AATACCTGCAAAGCCTTGAGA 15
CCL17_NM_002987 CATTCCCCTTAGAAAGCTGA 415 GTACTTCAAGGGAGCCATTCCCCTT
435 _human_252 AGAAAGCTGAAGACGTGGTA 16 CCL17_NM_002987
AGAGCTGAATTCAAAACCAG 416 CCGCCTGCTGATGGGAGAGCTGAAT 436 _human_51
TCAAAACCAGGGTGTCTCCC 17 CCL17_NM_002987 GATGGGAGAGCTGAATTCAA 417
GTGTCACCGCCTGCTGATGGGAGA 437 _human_45 GCTGAATTCAAAACCAGGGTG 18
CCL17_NM_002987 TGATGGGAGAGCTGAATTCA 418 AGTGTCACCGCCTGCTGATGGGAGA
438 _human_44 GCTGAATTCAAAACCAGGGT 19 CCL17_NM_002987
ACTTTGAGCTCACAGTGTCA 419 GCTCAGAGAGAAGTGACTTTGAGCT 439 _human_16
CACAGTGTCACCGCCTGCTG 20 CCL17_NM_002987 GAGTGAAGAATGCAGTTAAA 420
ACCCCAACAACAAGAGAGTGAAGA 440 _human_368 ATGCAGTTAAATACCTGCAAA
Accession: NM_002990 HUGO gene symbol: CCL22 1 CCL22_NM_002990
GTATTTGAAAACAGAGTAAA 441 GCTGGAGTTATATATGTATTTGAA 461 _human_2083
AACAGAGTAAATACTTAAGAG 2 CCL22_NM_002990 CAATAAGCTGAGCCAATGAA 442
GGTGAAGATGATTCTCAATAAGC 462 _human_298 TGAGCCAATGAAGAGCCTACTC 3
CCL22_NM_002990 TACTTAAGAGGCCAAATAGA 443 TGAAAACAGAGTAAATACTTAAG
463 _human_2103 AGGCCAAATAGATGAATGGAAG 4 CCL22_NM_002990
ATGTATTTGAAAACAGAGTA 444 AAGCTGGAGTTATATATGTATTTG 464 _human_2081
AAAACAGAGTAAATACTTAAG 5 CCL22_NM_002990 TTCATACAGCAAGTATGGGA 445
TTGAGAAATATTCTTTTCATACAG 465 _human_2496 CAAGTATGGGACAGCAGTGTC 6
CCL22_NM_002990 CTGCAGACAAAATCAATAAA 446 GAGCCCAGAAAGTGGCTGCAGAC
466 _human_1052 AAAATCAATAAAACTAATGTCC 7 CCL22_NM_002990
TGCAGACAAAATCAATAAAA 447 AGCCCAGAAAGTGGCTGCAGACA 467 _human_1053
AAATCAATAAAACTAATGTCCC 8 CCL22_NM_002990 GGCCAAATAGATGAATGGAA 448
AGTAAATACTTAAGAGGCCAAAT 468 _human_2112 AGATGAATGGAAGAATTTTAGG 9
CCL22_NM_002990 AATAAGCTGAGCCAATGAAG 449 GTGAAGATGATTCTCAATAAGCT
469 _human_299 GAGCCAATGAAGAGCCTACTCT 10 CCL22_NM_002990
AAGAGGCCAAATAGATGAAT 450 ACAGAGTAAATACTTAAGAGGCC 470 _human_2108
AAATAGATGAATGGAAGAATTT 11 CCL22_NM_002990 AAATAGATGAATGGAAGAAT 451
AATACTTAAGAGGCCAAATAGAT 471 _human_2116 GAATGGAAGAATTTTAGGAACT 12
CCL22_NM_002990 AAACAGAGTAAATACTTAAG 452 TATATATGTATTTGAAAACAGAGT
472 _human_2091 AAATACTTAAGAGGCCAAATA 13 CCL22_NM_002990
AGCTGGAGTTATATATGTAT 453 TGACTTGGTATTATAAGCTGGAG 473 _human_2067
TTATATATGTATTTGAAAACAG 14 CCL22_NM_002990 ACCTTTGACTTGGTATTATA 454
ATGGTGTGAAAGACTACCTTTGA 474 _human_2047 CTTGGTATTATAAGCTGGAGTT 15
CCL22_NM_002990 AACCTTCAGGGATAAGGAGA 455 TGGCGTGGTGTTGCTAACCTTCA
475 _human_238 GGGATAAGGAGATCTGTGCCGA 16 CCL22_NM_002990
GTGAAAGACTACCTTTGACT 456 AATTCATGCTATGGTGTGAAAGA 476 _human_2037
CTACCTTTGACTTGGTATTATA 17 CCL22_NM_002990 CTATGGTGTGAAAGACTACC 457
ACAATCAAATTCATGCTATGGTGT 477 _human_2030 GAAAGACTACCTTTGACTTGG 18
CCL22_NM_002990 CACTACGGCTGGCTAATTTT 458 ATTACAGGTGTGTGCCACTACGG
478 _human_1682 CTGGCTAATTTTTGTATTTTTA 19 CCL22_NM_002990
GGAGTTATATATGTATTTGA 459 TTGGTATTATAAGCTGGAGTTATA 479 _human_2071
TATGTATTTGAAAACAGAGTA 20 CCL22_NM_002990 ATATCAATACAGAGACTCAA 460
CCAAAAGGCAGTTACATATCAAT 480 _human_1111 ACAGAGACTCAAGGTCACTAGA
Accession: NM_005618 HUGO gene symbol: DLL1 1 DLL1_NM_005618
CTGTTTTGTTAATGAAGAAA 481 TATTTGAGTTTTTTACTGTTTTGTTA 501 _human_3246
ATGAAGAAATTCCTTTTTA 2 DLL1_NM_005618 TTGTATATAAATGTATTTAT 482
TGTGACTATATTTTTTTGTATATAAA 502 _human_3193 TGTATTTATGGAATATTGT 3
DLL1_NM_005618 TGTTTTGTTAATGAAGAAAT 483 ATTTGAGTTTTTTACTGTTTTGTTAA
503 _human_3247 TGAAGAAATTCCTTTTTAA 4 DLL1_NM_005618
AATTTTGGTAAATATGTACA 484 GTTTTTTATAATTTAAATTTTGGTAA 504 _human_3141
ATATGTACAAAGGCACTTC 5 DLL1_NM_005618 AAATTTTATGAATGACAAAA 485
ATATTTTTCCAAAATAAATTTTATGA 505 _human_3293 ATGACAAAAAAAAAAAAAA 6
DLL1_NM_005618 TTTATGGAATATTGTGCAAA 486 TTGTATATAAATGTATTTATGGAATA
506 _human_3208 TTGTGCAAATGTTATTTGA 7 DLL1_NM_005618
TTACTGTTTTGTTAATGAAG 487 TGTTATTTGAGTTTTTTACTGTTTTGT 507
_human_3243 TAATGAAGAAATTCCTTT 8 DLL1_NM_005618
TTCTTGAATTAGAAACACAA 488 TTATGAGCCAGTCTTTTCTTGAATTA 508 _human_2977
GAAACACAAACACTGCCTT 9 DLL1_NM_005618 CAGTTGCTCTTAAGAGAATA 489
CCGTTGCACTATGGACAGTTGCTCTT 509 _human_2874 AAGAGAATATATATTTAAA 10
DLL1_NM_005618 CAACTTCAAAAGACACCAAG 490 CGGACTCGGGCTGTTCAACTTCAAA
510 _human_2560 AGACACCAAGTACCAGTCGG 11 DLL1_NM_005618
TCCAAAATAAATTTTATGAA 491 TTTTTAAAATATTTTTCCAAAATAAA 511 _human_3285
TTTTATGAATGACAAAAAA 12 DLL1_NM_005618 GAACTGAATTACGCATAAGA 492
TATATTTAAATGGGTGAACTGAATT 512 _human_2909 ACGCATAAGAAGCATGCACT 13
DLL1_NM_005618 GGATTTTGTGACAAACCAGG 493 TGTGATGAGCAGCATGGATTTTGTG
513 _human_1173 ACAAACCAGGGGAATGCAAG
14 DLL1_NM_005618 TACTGTTTTGTTAATGAAGA 494
GTTATTTGAGTTTTTTACTGTTTTGTT 514 _human_3244 AATGAAGAAATTCCTTTT 15
DLL1_NM_005618 TTTGGTAAATATGTACAAAG 495 TTTTATAATTTAAATTTTGGTAAATA
515 _human_3144 TGTACAAAGGCACTTCGGG 16 DLL1_NM_005618
CCAAAATAAATTTTATGAAT 496 TTTTAAAATATTTTTCCAAAATAAAT 516 _human_3286
TTTATGAATGACAAAAAAA 17 DLL1_NM_005618 ATAATTTAAATTTTGGTAAA 497
TGATGTTCGTTTTTTATAATTTAAAT 517 _human_3133 TTTGGTAAATATGTACAAA 18
DLL1_NM_005618 AAATGGGTGAACTGAATTAC 498 AGAGAATATATATTTAAATGGGTGA
518 _human_2901 ACTGAATTACGCATAAGAAG 19 DLL1_NM_005618
TTCGGGTCTATGTGACTATA 499 TATGTACAAAGGCACTTCGGGTCTA 519 _human_3168
TGTGACTATATTTTTTTGTA 20 DLL1_NM_005618 ACTGTTTTGTTAATGAAGAA 500
TTATTTGAGTTTTTTACTGTTTTGTTA 520 _human_3245 ATGAAGAAATTCCTTTTT
Accession: NM_000639 HUGO gene symbol: FASLG 1 FASLG_NM_000639
TAGCTCCTCAACTCACCTAA 521 GGTTCAAAATGTCTGTAGCTCCTC 541 _human_1154
AACTCACCTAATGTTTATGAG 2 FASLG_NM_000639 ATGTTTTCCTATAATATAAT 522
TGTCAGCTACTAATGATGTTTTCC 542 _human_1771 TATAATATAATAAATATTTAT 3
FASLG_NM_000639 TTTTCCTATAATATAATAAA 523 CAGCTACTAATGATGTTTTCCTAT
543 _human_1774 AATATAATAAATATTTATGTA 4 FASLG_NM_000639
TTCCTATAATATAATAAATA 524 GCTACTAATGATGTTTTCCTATAA 544 _human_1776
TATAATAAATATTTATGTAGA 5 FASLG_NM_000639 TGCATTTGAGGTCAAGTAAG 525
GAGGGTCTTCTTACATGCATTTGA 545 _human_1086 GGTCAAGTAAGAAGACATGAA 6
FASLG_NM_000639 ATTGATTGTCAGCTACTAAT 526 TAGTGCTTAAAAATCATTGATTGT
546 _human_1750 CAGCTACTAATGATGTTTTCC 7 FASLG_NM_000639
AAATGAAAACATGTAATAAA 527 ATGTGCATTTTTGTGAAATGAAAA 547 _human_1820
CATGTAATAAAAAGTATATGT 8 FASLG_NM_000639 ATTGTGAAGTACATATTAGG 528
AGAGAGAATGTAGATATTGTGAA 548 _human_1659 GTACATATTAGGAAAATATGGG 9
FASLG_NM_000639 GCTTTCTGGAGTGAAGTATA 529 CTATGGAATTGTCCTGCTTTCTGG
549 _human_667 AGTGAAGTATAAGAAGGGTGG 10 FASLG_NM_000639
CATTTGGTCAAGATTTTGAA 530 GGAAAATATGGGTTGCATTTGGT 550 _human_1692
CAAGATTTTGAATGCTTCCTGA 11 FASLG_NM_000639 GGCTTATATAAGCTCTAAGA 531
TCTCAGACGTTTTTCGGCTTATAT 551 _human_986 AAGCTCTAAGAGAAGCACTTT 12
FASLG_NM_000639 ACCAGTGCTGATCATTTATA 532 GCAGTGTTCAATCTTACCAGTGCT
552 _human_911 GATCATTTATATGTCAACGTA 13 FASLG_NM_000639
CCATTTAACAGGCAAGTCCA 533 GCTGAGGAAAGTGGCCCATTTAA 553 _human_598
CAGGCAAGTCCAACTCAAGGTC 14 FASLG_NM_000639 AAGTACATATTAGGAAAATA 534
AATGTAGATATTGTGAAGTACAT 554 _human_1665 ATTAGGAAAATATGGGTTGCAT 15
FASLG_NM_000639 TGTGTGTGTGTATGACTAAA 535 GTGTGTGTGTGTGTGTGTGTGTG
555 _human_1625 TGTATGACTAAAGAGAGAATGT 16 FASLG_NM_000639
AAGAGGGAGAAGCATGAAAA 536 CTGGGCTGCCATGTGAAGAGGGA 556 _human_1238
GAAGCATGAAAAAGCAGCTACC 17 FASLG_NM_000639 GTGTATGACTAAAGAGAGAA 537
TGTGTGTGTGTGTGTGTGTATGA 557 _human_1632 CTAAAGAGAGAATGTAGATATT 18
FASLG_NM_000639 GTATTTCCAGTGCAATTGTA 538 CCTAACACAGCATGTGTATTTCCA
558 _human_1581 GTGCAATTGTAGGGGTGTGTG 19 FASLG_NM_000639
CAACTCTAATAGTGCTTAAA 539 ATGCTTCCTGACAATCAACTCTAA 559 _human_1726
TAGTGCTTAAAAATCATTGAT 20 FASLG_NM_000639 GTGTGTGTGTATGACTAAAG 540
TGTGTGTGTGTGTGTGTGTGTGT 560 human_1626 GTATGACTAAAGAGAGAATGTA
Accession: NM_001267706 HUGO gene symbol: CD274 1
CD274_NM_001267706 ACCTGCATTAATTTAATAAA 561
ATTGTCACTTTTTGTACCTGCATTA 581 _human_3222 ATTTAATAAAATATTCTTAT 2
CD274_NM_001267706 AACTTGCCCAAACCAGTAAA 562 GCAAACAGATTAAGTAACTTGCC
582 _human_1538 CAAACCAGTAAATAGCAGACCT 3 CD274_NM_001267706
ATTTGCTCACATCTAGTAAA 563 ACTTGCTGCTTAATGATTTGCTCA 583 _human_1218
CATCTAGTAAAACATGGAGTA 4 CD274_NM_001267706 CCTTTGCCATATAATCTAAT 564
TTTATTCCTGATTTGCCTTTGCCAT 584 _human_1998 ATAATCTAATGCTTGTTTAT 5
CD274_NM_001267706 ATATAGCAGATGGAATGAAT 565
ATTTTAGTGTTTCTTATATAGCAG 585 _human_2346 ATGGAATGAATTTGAAGTTCC 6
CD274_NM_001267706 GCCTTTGCCATATAATCTAA 566
ATTTATTCCTGATTTGCCTTTGCCA 586 _human_1997 TATAATCTAATGCTTGTTTA 7
CD274_NM_001267706 GATTTGCCTTTGCCATATAA 567
ATTATATTTATTCCTGATTTGCCTT 587 _human_1992 TGCCATATAATCTAATGCTT 8
CD274_NM_001267706 AATTTTCATTTACAAAGAGA 568
CTTAATAATCAGAGTAATTTTCAT 588 _human_1905 TTACAAAGAGAGGTCGGTACT 9
CD274_NM_001267706 AGTGTTTCTTATATAGCAGA 569
ATTTTTATTTATTTTAGTGTTTCTT 589 _human_2336 ATATAGCAGATGGAATGAAT 10
CD274_NM_001267706 GCTTTCTGTCAAGTATAAAC 570
GAACTTTTGTTTTCTGCTTTCTGTC 590 _human_2656 AAGTATAAACTTCACTTTGA 11
CD274_NM_001267706 CATTTGGAAATGTATGTTAA 571
TCTAAAGATAGTCTACATTTGGAA 591 _human_2235 ATGTATGTTAAAAGCACGTAT 12
CD274_NM_001267706 TTATTTTAGTGTTTCTTATA 572
CTTTGCTATTTTTATTTATTTTAGT 592 _human_2329 GTTTCTTATATAGCAGATGG 13
CD274_NM_001267706 GTGGTAGCCTACACACATAA 573
CAGCTTTACAATTATGTGGTAGCC 593 _human_1433 TACACACATAATCTCATTTCA 14
CD274_NM_001267706 ATGAGGAGATTAACAAGAAA 574 GGAGCTCATAGTATAATGAGGAG
594 _human_1745 ATTAACAAGAAAATGTATTATT 15 CD274_NM_001267706
CAATTTTGTCGCCAAACTAA 575 TTGTAGTAGATGTTACAATTTTGT 595 _human_1183
CGCCAAACTAAACTTGCTGCT 16 CD274_NM_001267706 TATATAGCAGATGGAATGAA
576 TATTTTAGTGTTTCTTATATAGCA 596 _human_2345 GATGGAATGAATTTGAAGTTC
17 CD274_NM_001267706 AAATGCCACTAAATTTTAAA 577
CTGTCTTTTCTATTTAAATGCCACT 597 _human_2069 AAATTTTAAATTCATACCTT 18
CD274_NM_001267706 TCTTTCCCATAGCTTTTCAT 578
TTTGTTTCTAAGTTATCTTTCCCAT 598 _human_2414 AGCTTTTCATTATCTTTCAT 19
CD274_NM_001267706 TATATTCATGACCTACTGGC 579
GATATTTGCTGTCTTTATATTCAT 599 _human_129 GACCTACTGGCATTTGCTGAA 20
CD274_NM_001267706 GTCCAGTGTCATAGCATAAG 580
TATTATTACAATTTAGTCCAGTGT 600 _human_1783 CATAGCATAAGGATGATGCGA
Accession: NM_002164 HUGO gene symbol: IDO1 1 IDO1_NM_002164
ATTCTGTCATAATAAATAAA 601 AAAAAAAAAAGATATATTCTGTCA 621 _human_1896
TAATAAATAAAAATGCATAAG 2 IDO1_NM_002164 TATCTTATCATTGGAATAAA 602
AAGTTTTGTAATCTGTATCTTATCA 622 _human_1532 TTGGAATAAAATGACATTCA 3
IDO1_NM_002164 GTGATGGAGACTGCAGTAAA 603 TTTTGTTCTCATTTCGTGATGGAGA
623 _human_578 CTGCAGTAAAGGATTCTTCC 4 IDO1_NM_002164
TTCTGTCATAATAAATAAAA 604 AAAAAAAAAGATATATTCTGTCAT 624 _human_1897
AATAAATAAAAATGCATAAGA 5 IDO1_NM_002164 CTTGTAGGAAAACAACAAAA 605
AATACCTGTGCATTTCTTGTAGGAA 625 _human_1473 AACAACAAAAGGTAATTATG 6
IDO1_NM_002164 ATAAAATGACATTCAATAAA 606 TATCTTATCATTGGAATAAAATGAC
626 _human_1547 ATTCAATAAATAAAAATGCA 7 IDO1_NM_002164
CGTAAGGTCTTGCCAAGAAA 607 GGTCATGGAGATGTCCGTAAGGTC 627 _human_412
TTGCCAAGAAATATTGCTGTT 8 IDO1_NM_002164 TCTTGTAGGAAAACAACAAA 608
AAATACCTGTGCATTTCTTGTAGGA 628 _human_1472 AAACAACAAAAGGTAATTAT 9
IDO1_NM_002164 AACTGGAGGCACTGATTTAA 609 ACTGGAAGCCAAAGGAACTGGAG 629
_human_1248 GCACTGATTTAATGAATTTCCT 10 IDO1_NM_002164
CAATACAAAAGACCTCAAAA 610 GTTTTACCAATAATGCAATACAAAA 630 _human_1440
GACCTCAAAATACCTGTGCA 11 IDO1_NM_002164 TGCTTCTGCAATCAAAGTAA 611
GGTGGAAATAGCAGCTGCTTCTGC 631 _human_636 AATCAAAGTAATTCCTACTGT 12
IDO1_NM_002164 AATGACATTCAATAAATAAA 612 TTATCATTGGAATAAAATGACATTC
632 _human_1551 AATAAATAAAAATGCATAAG 13 IDO1_NM_002164
ATCATTGGAATAAAATGACA 613 TGTAATCTGTATCTTATCATTGGAA 633 _human_1538
TAAAATGACATTCAATAAAT 14 IDO1_NM_002164 ACCAATAATGCAATACAAAA 614
ACTATGCAATGTTTTACCAATAATG 634 _human_1430 CAATACAAAAGACCTCAAAA 15
IDO1_NM_002164 ATCTGTATCTTATCATTGGA 615 ACTAGAAGTTTTGTAATCTGTATCT
635 _human_1527 TATCATTGGAATAAAATGAC 16 IDO1_NM_002164
ATCTTATCATTGGAATAAAA 616 AGTTTTGTAATCTGTATCTTATCAT 636 _human_1533
TGGAATAAAATGACATTCAA 17 IDO1_NM_002164 CAGCTGCTTCTGCAATCAAA 617
TATTGGTGGAAATAGCAGCTGCTT 637 _human_632 CTGCAATCAAAGTAATTCCTA 18
IDO1_NM_002164 GCAATACAAAAGACCTCAAA 618 TGTTTTACCAATAATGCAATACAAA
638 _human_1439 AGACCTCAAAATACCTGTGC 19 IDO1_NM_002164
TCCTACTGTATTCAAGGCAA 619 TGCAATCAAAGTAATTCCTACTGTA 639 _human_657
TTCAAGGCAATGCAAATGCA 20 IDO1_NM_002164 CAGAGCCACAAACTAATACT 620
CATTACCCATTGTAACAGAGCCAC 640 _human_1398 AAACTAATACTATGCAATGTT
Accession: NM_001558 HUGO gene symbol: IL10RA 1 IL10RA_NM_001558_
TTGTTCATTTATTTATTGGA 641 CTTTATTTATTTATTTTGTTCATTT 661 human_3364
ATTTATTGGAGAGGCAGCAT 2 IL10RA_NM_001558_ TTATTCCAATAAATTGTCAA 642
AGTGATACATGTTTTTTATTCCAA 662 human_3626 TAAATTGTCAAGACCACAGGA 3
IL10RA_NM_001558_ TATTTTCTGGACACTCAAAC 643 AGATCTTAAGGTATATATTTTCTG
663 human_2395 GACACTCAAACACATCATAAT 4 IL10RA_NM_001558_
TTTATTGGAGAGGCAGCATT 644 TATTTTGTTCATTTATTTATTGGAG 664 human_3375
AGGCAGCATTGCACAGTGAA 5 IL10RA_NM_001558_ ACCTTGGAGAAGTCACTTAT 645
GTTTCCAGTGGTATGACCTTGGA 665 human_3469 GAAGTCACTTATCCTCTTGGAG 6
IL10RA_NM_001558_ TTATTTATTTATTTTGTTCA 646
GTTCCCTTGAAAGCTTTATTTATTT 666 human_3351 ATTTTGTTCATTTATTTATT
7 IL10RA_NM_001558_ CTCTTTCCTGTATCATAAAG 647
TCTCCCTCCTAGGAACTCTTTCCT 667 human_2108 GTATCATAAAGGATTATTTGC 8
IL10RA_NM_001558_ CTGAGGAAATGGGTATGAAT 648 GGATGTGAGGTTCTGCTGAGGAA
668 human_3563 ATGGGTATGAATGTGCCTTGAA 9 IL10RA_NM_001558_
GAATGTGCCTTGAACACAAA 649 TGAGGAAATGGGTATGAATGTGC 669 human_3579
CTTGAACACAAAGCTCTGTCAA 10 IL10RA_NM_001558_ GGACACTCAAACACATCATA
650 AGGTATATATTTTCTGGACACTCA 670 human_2403 AACACATCATAATGGATTCAC
11 IL10RA_NM_001558_ CTGTATCATAAAGGATTATT 651
CCTAGGAACTCTTTCCTGTATCAT 671 human_2115 AAAGGATTATTTGCTCAGGGG 12
IL10RA_NM_001558_ TCACTTCCGAGAGTATGAGA 652 TGAAAGCATCTTCAGTCACTTCCG
672 human_563 AGAGTATGAGATTGCCATTCG 13 IL10RA_NM_001558_
TCTCTGGAGCATTCTGAAAA 653 TCTCAGCCCTGCCTTTCTCTGGAG673 human_3197
CATTCTGAAAACAGATATTCT 14 IL10RA_NM_001558_ TTATGCCAGAGGCTAACAGA 654
AAGCTGGCTTGTTTCTTATGCCAG 674 human_2987 AGGCTAACAGATCCAATGGGA 15
IL10RA_NM_001558_ AGTGGCATTGACTTAGTTCA 655 AGGGGCCAGGATGACAGTGGCA
675 human_1278 TTGACTTAGTTCAAAACTCTGAG 16 IL10RA_NM_001558_
TTTCTGGACACTCAAACACA 656 TCTTAAGGTATATATTTTCTGGAC 676 human_2398
ACTCAAACACATCATAATGGA 17 IL10RA_NM_001558_ GCATTGCACAGTGAAAGAAT 657
TTTATTGGAGAGGCAGCATTGCA 677 human_3390 CAGTGAAAGAATTCTGGATATC 18
IL10RA_NM_001558_ GACCTTGGAGAAGTCACTTA 658 TGTTTCCAGTGGTATGACCTTGGA
678 human_3468 GAAGTCACTTATCCTCTTGGA 19 IL10RA_NM_001558_
TCACGTTCACACACAAGAAA 659 AGGTGCCGGGAAACTTCACGTTC 679 human_610
ACACACAAGAAAGTAAAACATG 20 IL10RA_NM_001558_ ACTTTGCTGTTTCCAGTGGT
660 GAAATTCTAGCTCTGACTTTGCTG 680 human_3446 TTTCCAGTGGTATGACCTTGG
Accession: NM_000214 HUGO gene symbol: JAG1 1 JAG1_NM_000214
TATTTGATTTATTAACTTAA 681 ATTAATCACTGTGTATATTTGATTT 701 _human_4799
ATTAACTTAATAATCAAGAG 2 JAG1_NM_000214 GAAAAGTAATATTTATTAAA 682
TTGGCAATAAATTTTGAAAAGTAA 702 _human_5658 TATTTATTAAATTTTTTTGTA 3
JAG1_NM_000214 ACTTTGTATAGTTATGTAAA 683 AATGTCAAAAGTAGAACTTTGTAT
703 _human_4752 AGTTATGTAAATAATTCTTTT 4 JAG1_NM_000214
GAATACTTGAACCATAAAAT 684 TCTAATAAGCTAGTTGAATACTTGA 704 _human_5418
ACCATAAAATGTCCAGTAAG 5 JAG1_NM_000214 TCTTGGCAATAAATTTTGAA 685
TCTTTGATGTGTTGTTCTTGGCAAT 705 _human_5641 AAATTTTGAAAAGTAATATT 6
JAG1_NM_000214 TTTCTGCTTTAGACTTGAAA 686 TGTTTGTTTTTTGTTTTTCTGCTTTA
706 _human_5150 GACTTGAAAAGAGACAGGC 7 JAG1_NM_000214
TATATTTATTGACTCTTGAG 687 GATCATAGTTTTATTTATATTTATT 707 _human_4526
GACTCTTGAGTTGTTTTTGT 8 JAG1_NM_000214 TATGATGACGTACAAGTAGT 688
TTTGTATATTGGTTTTATGATGACG 708 _human_4566 TACAAGTAGTTCTGTATTTG 9
JAG1_NM_000214 GTGTTGTTCTTGGCAATAAA 689 AAATGCATCTTTGATGTGTTGTTCT
709 _human_5634 TGGCAATAAATTTTGAAAAG 10 JAG1_NM_000214
CTGATCTAAAAGGGAATAAA 690 CCTTTTTCCATGCAGCTGATCTAAA 710 _human_173
AGGGAATAAAAGGCTGCGCA 11 JAG1_NM_000214 TACGACGTCAGATGTTTAAA 691
GATGGAATTTTTTTGTACGACGTCA 711 _human_5031 GATGTTTAAAACACCTTCTA 12
JAG1_NM_000214 AATAATCAAGAGCCTTAAAA 692 TTGATTTATTAACTTAATAATCAAG
712 _human_4817 AGCCTTAAAACATCATTCCT 13 JAG1_NM_000214
GTATGAAAACATGGAACAGT 693 TTATTAAATTTTTTTGTATGAAAAC 713 _human_5685
ATGGAACAGTGTGGCCTCTT 14 JAG1_NM_000214 TGGTTTTATGATGACGTACA 694
GTTGTTTTTGTATATTGGTTTTATG 714 _human_4560 ATGACGTACAAGTAGTTCTG 15
JAG1_NM_000214 TTCTGCTTTAGACTTGAAAA 695 GTTTGTTTTTTGTTTTTCTGCTTTAG
715 _human_5151 ACTTGAAAAGAGACAGGCA 16 JAG1_NM_000214
CTTGGCAATAAATTTTGAAA 696 CTTTGATGTGTTGTTCTTGGCAATA 716 _human_5642
AATTTTGAAAAGTAATATTT 17 JAG1_NM_000214 TTTAATCTACTGCATTTAGG 697
GATTTGATTTTTTTTTTTAATCTACT 717 _human_5377 GCATTTAGGGAGTATTCTA 18
JAG1_NM_000214 TGTATAGTTATGTAAATAAT 698 TCAAAAGTAGAACTTTGTATAGTTA
718 _human_4756 TGTAAATAATTCTTTTTTAT 19 JAG1_NM_000214
ATTTATATTTATTGACTCTT 699 TTAGATCATAGTTTTATTTATATTTA 719 _human_4523
TTGACTCTTGAGTTGTTTT 20 JAG1_NM_000214 CTTTTCACCATTCGTACATA 700
TGTAAATTCTGATTTCTTTTCACCAT 720 _human_5325 TCGTACATAATACTGAACC
Accession: NM_002226 HUGO gene symbol: JAG2 1 JAG2_NM_002226
CGTTTCTTTAACCTTGTATA 721 AATGTTTATTTTCTACGTTTCTTTAA 741 _human_4266
CCTTGTATAAATTATTCAG 2 JAG2_NM_002226 TAAATGAATGAACGAATAAA 722
GGCAGAACAAATGAATAAATGAAT 742 _human_5800 GAACGAATAAAAATTTTGACC 3
JAG2_NM_002226 TCATTCATTTATTCCTTTGT 723 GGTCAAAATTTTTATTCATTCATTT
743 _human_5450 ATTCCTTTGTTTTGCTTGGT 4 JAG2_NM_002226
GTAAATGTGTACATATTAAA 724 TGAAAGTGCATTTTTGTAAATGTGT 744 _human_5021
ACATATTAAAGGAAGCACTC 5 JAG2_NM_002226 ACCCACGAATACGTATCAAG 725
AGTATAAAATTGCTTACCCACGAAT 745 _human_5398 ACGTATCAAGGTCTTAAGGA 6
JAG2_NM_002226 GTTTTATAAAATAGTATAAA 726 AAACAGCTGAAAACAGTTTTATAA
746 _human_5371 AATAGTATAAAATTGCTTACC 7 JAG2_NM_002226
CAACTGAGTCAAGGAGCAAA 727 TGAGGGGTAGGAGGTCAACTGAG 747 _human_5691
TCAAGGAGCAAAGCCAAGAACC 8 JAG2_NM_002226 ATGTGTACATATTAAAGGAA 728
AGTGCATTTTTGTAAATGTGTACAT 748 _human_5025 ATTAAAGGAAGCACTCTGTA 9
JAG2_NM_002226 TTCTTTAACCTTGTATAAAT 729 GTTTATTTTCTACGTTTCTTTAACCT
749 _human_4269 TGTATAAATTATTCAGTAA 10 JAG2_NM_002226
ATTTTCTACGTTTCTTTAAC 730 AAAAACCAAATGTTTATTTTCTACG 750 _human_4258
TTTCTTTAACCTTGTATAAA 11 JAG2_NM_002226 CAGTTTTATAAAATAGTATA 731
TAAAACAGCTGAAAACAGTTTTAT 751 _human_5369 AAAATAGTATAAAATTGCTTA 12
JAG2_NM_002226 GCACAGGCAGAACAAATGAA 732 GAGTGAGGCTGCCTTGCACAGGCA
752 _human_5780 GAACAAATGAATAAATGAATG 13 JAG2_NM_002226
TCAGGCTGAAAACAATGGAG 733 ATTATTCAGTAACTGTCAGGCTGA 753 _human_4302
AAACAATGGAGTATTCTCGGA 14 JAG2_NM_002226 TAAAATTGCTTACCCACGAA 734
TTTTATAAAATAGTATAAAATTGCT 754 _human_5387 TACCCACGAATACGTATCAA 15
JAG2_NM_002226 GTCAGGCTGAAAACAATGGA 735 AATTATTCAGTAACTGTCAGGCTG
755 _human_4301 AAAACAATGGAGTATTCTCGG 16 JAG2_NM_002226
AAATGTGTACATATTAAAGG 736 AAAGTGCATTTTTGTAAATGTGTAC 756 _human_5023
ATATTAAAGGAAGCACTCTG 17 JAG2_NM_002226 CAGTAACTGTCAGGCTGAAA 737
CTTGTATAAATTATTCAGTAACTGT 757 _human_4293 CAGGCTGAAAACAATGGAGT 18
JAG2_NM_002226 GTATTCTCGGATAGTTGCTA 738 GCTGAAAACAATGGAGTATTCTCG
758 _human_4321 GATAGTTGCTATTTTTGTAAA 19 JAG2_NM_002226
TCTCACACAAATTCACCAAA 739 AGGCGGAGAAGTTCCTCTCACACA 759 _human_3994
AATTCACCAAAGATCCTGGCC 20 JAG2_NM_002226 TTGTTTTGCTTGGTCATTCA 740
CATTCATTTATTCCTTTGTTTTGCTT 760 _human_5466 GGTCATTCAGAGGCAAGGT
Accession: NM_001315 HUGO gene symbol: MAPK14 1 MAPK14_NM_001315
TCATGCGAAAAGAACCTACA 761 ATTTCAGTCCATCATTCATGCGAAAA 781 _human_670
GAACCTACAGAGAACTGCG 2 MAPK14_NM_001315 AAATGTCAGAAGCTTACAGA 762
CTGAACAACATTGTGAAATGTCAGA 782 _human_833 AGCTTACAGATGACCATGTT 3
MAPK14_NM_001315 AAACATATGAAACATGAAAA 763 GAACTGCGGTTACTTAAACATATGA
783 _human_707 AACATGAAAATGTGATTGGT 4 MAPK14_NM_001315
CAGTTCCTTATCTACCAAAT 764 ACAGATGACCATGTTCAGTTCCTTAT 784 _human_863
CTACCAAATTCTCCGAGGT 5 MAPK14_NM_001315 TCCTGGTACAGACCATATTA 765
TGGAAGAACATTGTTTCCTGGTACA 785 _human_1150 GACCATATTAACCAGCTTCA 6
MAPK14_NM_001315 TTCCTTATCTACCAAATTCT 766
GATGACCATGTTCAGTTCCTTATCTA 786 _human_866 CCAAATTCTCCGAGGTCTA 7
MAPK14_NM_001315 TTCCTGGTACAGACCATATT 767 CTGGAAGAACATTGTTTCCTGGTAC
787 _human_1149 AGACCATATTAACCAGCTTC 8 MAPK14_NM_001315
AAGTATATACATTCAGCTGA 768 ATTCTCCGAGGTCTAAAGTATATAC 788 _human_896
ATTCAGCTGACATAATTCAC 9 MAPK14_NM_001315 CATTACAACCAGACAGTTGA 769
ATGCTGAACTGGATGCATTACAACC 789 _human_1076 AGACAGTTGATATTTGGTCA 10
MAPK14_NM_001315 AGGGACCTAAAACCTAGTAA 770 GCTGACATAATTCACAGGGACCTAA
790 _human_926 AACCTAGTAATCTAGCTGTG 11 MAPK14_NM_001315
CTCTGGAGGAATTCAATGAT 771 TTACACCTGCAAGGTCTCTGGAGGA 791 _human_765
ATTCAATGATGTGTATCTGG 12 MAPK14_NM_001315 TAAACATATGAAACATGAAA 772
AGAACTGCGGTTACTTAAACATATG 792 _human_706 AAACATGAAAATGTGATTGG 13
MAPK14_NM_001315 GATCTGAACAACATTGTGAA 773 CATCTCATGGGGGCAGATCTGAACA
793 _human_815 ACATTGTGAAATGTCAGAAG 14 MAPK14_NM_001315
TCAGTTCCTTATCTACCAAA 774 TACAGATGACCATGTTCAGTTCCTTA 794 _human_862
TCTACCAAATTCTCCGAGG 15 MAPK14_NM_001315 ATAATTCACAGGGACCTAAA 775
ATACATTCAGCTGACATAATTCACA 795 _human_917 GGGACCTAAAACCTAGTAAT 16
MAPK14_NM_001315 CGAGGTCTAAAGTATATACA 776 ATCTACCAAATTCTCCGAGGTCTAA
796 _human_887 AGTATATACATTCAGCTGAC 17 MAPK14_NM_001315
GAAATGTCAGAAGCTTACAG 777 TCTGAACAACATTGTGAAATGTCAG 797 _human_832
AAGCTTACAGATGACCATGT 18 MAPK14_NM_001315 AGCTGTTGACTGGAAGAACA 778
GATGCATAATGGCCGAGCTGTTGAC 798 _human_1125 TGGAAGAACATTGTTTCCTG 19
MAPK14_NM_001315 AAATTCTCCGAGGTCTAAAG 779
AGTTCCTTATCTACCAAATTCTCCGA 799 _human_879 GGTCTAAAGTATATACATT 20
MAPK14_NM_001315 AATGTGATTGGTCTGTTGGA 780 CATATGAAACATGAAAATGTGATTG
800 _human_725 GTCTGTTGGACGTTTTTACA
Accession: NM_003745 HUGO gene symbol: SOCS1 1 SOCS1_NM_003745
CTGCTGTGCAGAATCCTATT 801 TCTGGCTTTATTTTTCTGCTGTGCAGAA 821
_human_1141 TCCTATTTTATATTTTT 2 SOCS1_NM_003745
GCTGTGCAGAATCCTATTTT 802 TGGCTTTATTTTTCTGCTGTGCAGAATC 822
_human_1143 CTATTTTATATTTTTTA 3 SOCS1_NM_003745
TTAAAGTCAGTTTAGGTAAT 803 CCTATTTTATATTTTTTAAAGTCAGTTT 823
_human_1170 AGGTAATAAACTTTATT 4 SOCS1_NM_003745
CTGTGCAGAATCCTATTTTA 804 GGCTTTATTTTTCTGCTGTGCAGAATCC 824
_human_1144 TATTTTATATTTTTTAA 5 SOCS1_NM_003745
GTTTACATATACCCAGTATC 805 CTCCTACCTCTTCATGTTTACATATACC 825
_human_1076 CAGTATCTTTGCACAAA 6 SOCS1_NM_003745
ATTTTGTTATTACTTGCCTG 806 CTGGGATGCCGTGTTATTTTGTTATTA 826 _human_837
CTTGCCTGGAACCATGTG 7 SOCS1_NM_003745 TAACTGGGATGCCGTGTTAT 807
CCGTGCACGCAGCATTAACTGGGATG 827 _human_819 CCGTGTTATTTTGTTATTA 8
SOCS1_NM_003745 TGTTATTACTTGCCTGGAAC 808
GATGCCGTGTTATTTTGTTATTACTTGC 828 _human_841 CTGGAACCATGTGGGTA 9
SOCS1_NM_003745 TTTCTGCTGTGCAGAATCCT 809
GTCTCTGGCTTTATTTTTCTGCTGTGCA 829 _human_1138 GAATCCTATTTTATATT 10
SOCS1_NM_003745 CGTGTTATTTTGTTATTACT 810
CATTAACTGGGATGCCGTGTTATTTTG 830 _human_831 TTATTACTTGCCTGGAAC 11
SOCS1_NM_003745 TTTTAAAGTCAGTTTAGGTA 811
ATCCTATTTTATATTTTTTAAAGTCAGT 831 _human_1168 TTAGGTAATAAACTTTA 12
SOCS1_NM_003745 TGCTGTGCAGAATCCTATTT 812
CTGGCTTTATTTTTCTGCTGTGCAGAAT 832 _human_1142 CCTATTTTATATTTTTT 13
SOCS1_NM_003745 GGATGCCGTGTTATTTTGTT 813
ACGCAGCATTAACTGGGATGCCGTGTT 833 _human_825 ATTTTGTTATTACTTGCC 14
SOCS1_NM_003745 TTTAAAGTCAGTTTAGGTAA 814
TCCTATTTTATATTTTTTAAAGTCAGTT 834 _human_1169 TAGGTAATAAACTTTAT 15
SOCS1_NM_003745 TAAAGTCAGTTTAGGTAATA 815
CTATTTTATATTTTTTAAAGTCAGTTTA 835 _human_1171 GGTAATAAACTTTATTA 16
SOCS1_NM_003745 TCTGCTGTGCAGAATCCTAT 816
CTCTGGCTTTATTTTTCTGCTGTGCAGA 836 _human_1140 ATCCTATTTTATATTTT 17
SOCS1_NM_003745 ATATACCCAGTATCTTTGCA 817
CCTCTTCATGTTTACATATACCCAGTAT 837 _human_1082 CTTTGCACAAACCAGGG 18
SOCS1_NM_003745 AGAATCCTATTTTATATTTT 818
ATTTTTCTGCTGTGCAGAATCCTATTTT 838 _human_1150 ATATTTTTTAAAGTCAG 19
SOCS1_NM_003745 GGTTGTTGTAGCAGCTTAAC 819
CCTCTGGGTCCCCCTGGTTGTTGTAGC 839 _human_1011 AGCTTAACTGTATCTGGA 20
SOCS1_NM_003745 CCCAGTATCTTTGCACAAAC 820 TCATGTTTACATATACCCAGTAT
840 _human_1087 CTTTGCACAAACCAGGGGTTGG Accession: NM_003150 HUGO
gene symbol: STAT3 1 STAT3_NM_003150 ATATTGCTGTATCTACTTTA 841
TTTTTTTTTTTTGGTATATTGCTGT 861 _human_4897 ATCTACTTTAACTTCCAGAA 2
STAT3_NM_003150 TGTTTGTTAAATCAAATTAG 842 GTTTCTGTGGAATTCTGTTTGTTA
862 _human_4325 AATCAAATTAGCTGGTCTCTG 3 STAT3_NM_003150
TTTATCTAAATGCAAATAAG 843 TGTGGGTGATCTGCTTTTATCTAA 863 _human_2730
ATGCAAATAAGGATGTGTTCT 4 STAT3_NM_003150 ATTTTCCTTTGTAATGTATT 844
TTTATAAATAGACTTATTTTCCTTT 864 _human_3615 GTAATGTATTGGCCTTTTAG 5
STAT3_NM_003150 TATCAGCACAATCTACGAAG 845 GAGTCGAATGTTCTCTATCAGCAC
865 _human_453 AATCTACGAAGAATCAAGCAG 6 STAT3_NM_003150
AGCTTAACTGATAAACAGAA 846 CTTCAGTACATAATAAGCTTAACT 866 _human_4477
GATAAACAGAATATTTAGAAA 7 STAT3_NM_003150 GTTGTTGTTGTTCTTAGACA 847
CAGCTTTTTGTTATTGTTGTTGTTG 867 _human_2870 TTCTTAGACAAGTGCCTCCT 8
STAT3_NM_003150 GTTGTTGTTCTTAGACAAGT 848 CTTTTTGTTATTGTTGTTGTTGTTC
868 _human_2873 TTAGACAAGTGCCTCCTGGT 9 STAT3_NM_003150
TCTGTATTTAAGAAACTTAA 849 TATCAGCATAGCCTTTCTGTATTT 869 _human_3096
AAGAAACTTAAGCAGCCGGGC 10 STAT3_NM_003150 TTATTTTCCTTTGTAATGTA 850
TTTTTATAAATAGACTTATTTTCCT 870 _human_3613 TTGTAATGTATTGGCCTTTT 11
STAT3_NM_003150 TAACTGATAAACAGAATATT 851 AGTACATAATAAGCTTAACTGATA
871 _human_4481 AACAGAATATTTAGAAAGGTG 12 STAT3_NM_003150
ACATTCTGGGCACAAACACA 852 GATCCCGGAAATTTAACATTCTGG 872 _human_1372
GCACAAACACAAAAGTGATGA 13 STAT3_NM_003150 GTGATCTGCTTTTATCTAAA 853
AATGAGTGAATGTGGGTGATCTG 873 _human_2720 CTTTTATCTAAATGCAAATAAG 14
STAT3_NM_003150 CAGACCCGTCAACAAATTAA 854 GCAGAATCTCAACTTCAGACCCGT
874 _human_1044 CAACAAATTAAGAAACTGGAG 15 STAT3_NM_003150
GGAGCTGTTTAGAAACTTAA 855 GGAGGAGAGAATCGTGGAGCTG 875 _human_1148
TTTAGAAACTTAATGAAAAGTGC 16 STAT3_NM_003150 ACCATTGGGTTTAAATCATA 856
GTGAGACTTGGGCTTACCATTGG 876 _human_4523 GTTTAAATCATAGGGACCTAGG 17
STAT3_NM_003150 GGAGAATCTAAGCATTTTAG 857 AATAGGAAGGTTTAAGGAGAATC
877 _human_3573 TAAGCATTTTAGACTTTTTTTT 18 STAT3_NM_003150
CCTTGCTGACATCCAAATAG 858 CATTGCACTTTTTAACCTTGCTGA 878 _human_2987
CATCCAAATAGAAGATAGGAC 19 STAT3_NM_003150 AAATTAAGAAATAATAACAA 859
CCTAGGTTTCTTTTTAAATTAAGA 879 _human_3041 AATAATAACAATTAAAGGGCA 20
STAT3_NM_003150 TTTTAAATTAAGAAATAATA 860 AAGCCCTAGGTTTCTTTTTAAATT
880 _human_3037 AAGAAATAATAACAATTAAAG Accession: NM_006290 HUGO
gene symbol: TNFAIP3 1 TNFAIP3_NM_006290 AGCTTGAACTGAGGAGTAAA 881
ACTTCTAAAGAAGTTAGCTTGAAC 901 _human_3451 TGAGGAGTAAAAGTGTGTACA 2
TNFAIP3_NM_006290 CCTTTGCAACATCCTCAGAA 882 AATACACATATTTGTCCTTTGCAA
902 _human_916 CATCCTCAGAAGGCCAATCAT 3 TNFAIP3_NM_006290
TTCTTTCCAAAGATACCAAA 883 ACGAATCTTTATAATTTCTTTCCAA 903 _human_4422
AGATACCAAATAAACTTCAG 4 TNFAIP3_NM_006290 TTATTTTATTACAAACTTCA 884
TGTAATTCACTTTATTTATTTTATT 904 _human_3688 ACAAACTTCAAGATTATTTA 5
TNFAIP3_NM_006290 TATTTATACTTATTATAAAA 885 GTGAAAAAAAGTAATTATTTATAC
905 _human_4536 TTATTATAAAAAGTATTTGAA 6 TNFAIP3_NM_006290
CATTTCAGACAAAATGCTAA 886 AAGGCCAATCATTGTCATTTCAGA 906 _human_949
CAAAATGCTAAGAAGTTTGGA 7 TNFAIP3_NM_006290 ATGAAGGAGAAGCTCTTAAA 887
GATCCTGAAAATGAGATGAAGGA 907 _human_1214 GAAGCTCTTAAAAGAGTACTTA 8
TNFAIP3_NM_006290 ATTTTGTGTTGATCATTATT 888 AGTTGATATCTTAATATTTTGTGT
908 _human_4489 TGATCATTATTTCCATTCTTA 9 TNFAIP3_NM_006290
TTCATCGAGTACAGAGAAAA 889 TTTTGCACACTGTGTTTCATCGAG 909 _human_2204
TACAGAGAAAACAAACATTTT 10 TNFAIP3_NM_006290 TTACTGGGAAGACGTGTAAC 890
AAAAATTAGAATATTTTACTGGGA 910 _human_3394 AGACGTGTAACTCTTTGGGTT 11
TNFAIP3_NM_006290 TCATTGAAGCTCAGAATCAG 891 ACTGCCAGAAGTGTTTCATTGAA
911 _human_2355 GCTCAGAATCAGAGATTTCATG 12 TNFAIP3_NM_006290
TTCCATTCTTAATGTGAAAA 892 TGTGTTGATCATTATTTCCATTCTT 912 _human_4508
AATGTGAAAAAAAGTAATTA 13 TNFAIP3_NM_006290 TGAAGGATACTGCCAGAAGT 893
TGGAAGCACCATGTTTGAAGGAT 913 _human_2332 ACTGCCAGAAGTGTTTCATTGA 14
TNFAIP3_NM_006290 CACAAGAGTCAACATTAAAA 894 ATAAATGTAACTTTTCACAAGAGT
914 _human_4650 CAACATTAAAAAATAAATTAT 15 TNFAIP3_NM_006290
AATTATTTATACTTATTATA 895 AATGTGAAAAAAAGTAATTATTTA 915 _human_4533
TACTTATTATAAAAAGTATTT 16 TNFAIP3_NM_006290 TTCGTGCTTCTCCTTATGAA 896
CATATTCATCGATGTTTCGTGCTT 916 _human_3907 CTCCTTATGAAACTCCAGCTA 17
TNFAIP3_NM_006290 TATTTTATTACAAACTTCAA 897
GTAATTCACTTTATTTATTTTATTA 917 _human_3689 CAAACTTCAAGATTATTTAA 18
TNFAIP3_NM_006290 TATTACAAACTTCAAGATTA 898
TCACTTTATTTATTTTATTACAAAC 918 _human_3694 TTCAAGATTATTTAAGTGAA 19
TNFAIP3_NM_006290 CTCTTAAAGTTGATATCTTA 899
TGTTTTCATCTAATTCTCTTAAAGT 919 _human_4467 TGATATCTTAATATTTTGTG 20
TNFAIP3_NM_006290 TTCCAAAGATACCAAATAAA 900
ATCTTTATAATTTCTTTCCAAAGAT 920 _human_4426 ACCAAATAAACTTCAGTGTT
Accession: NM_003326 HUGO gene symbol: TNFSF4 1 TNFSF4_NM_003326
AATTTGACTTAGCCACTAAC 921 GAGATCAGAATTTTAAATTTGACT 941 _human_2984
TAGCCACTAACTAGCCATGTA 2 TNFSF4_NM_003326 GATATTAATAATATAGTTAA 922
GAGAGTATTAATATTGATATTAAT 942 _human_3422 AATATAGTTAATAGTAATATT 3
TNFSF4_NM_003326 CTGTGAATGCACATATTAAA 923 TGCTTACAGTGTTATCTGTGAATG
943 _human_3119 CACATATTAAATGTCTATGTT 4 TNFSF4_NM_003326
GTTTTCTATTTCCTCTTAAG 924 GGATTTTTTTTTCCTGTTTTCTATT 944 _human_2208
TCCTCTTAAGTACACCTTCA 5 TNFSF4_NM_003326 AAATAGCACTAAGAAGTTAT 925
ATTCAATCTGATGTCAAATAGCAC 945 _human_1727 TAAGAAGTTATTGTGCCTTAT 6
TNFSF4_NM_003326 CCAATCCCGATCCAAATCAT 926 AATGCTTAAGGGATTCCAATCCC
946 _human_3311 GATCCAAATCATAATTTGTTCT 7 TNFSF4_NM_003326
CTATTTAGAGAATGCTTAAG 927 TTAGTTAGATATTTTCTATTTAGA 947 _human_3286
GAATGCTTAAGGGATTCCAAT 8 TNFSF4_NM_003326 CAGTTTGCATATTGCCTAAA 928
AGGTTAAATTGATTGCAGTTTGCA 948 _human_1222 TATTGCCTAAATTTAAACTTT 9
TNFSF4_NM_003326 CTCGAATTCAAAGTATCAAA 929 TATCACATCGGTATCCTCGAATTC
949 _human_326 AAAGTATCAAAGTACAATTTA 10 TNFSF4_NM_003326
ATCTGTGAATGCACATATTA 930 TATGCTTACAGTGTTATCTGTGAA 950 _human_3117
TGCACATATTAAATGTCTATG 11 TNFSF4_NM_003326 TTTGTGGGAAAAGAATTGAA 931
TATACATGGCAGAGTTTTGTGGG 951 _human_2938 AAAAGAATTGAATGAAAAGTCA 12
TNFSF4_NM_003326 ATTGACCATGTTCTGCAAAA 932 ATTTCACTTTTTGTTATTGACCATG
952
_human_2537 TTCTGCAAAATTGCAGTTAC 13 TNFSF4_NM_003326
GATTCTTCATTGCAAGTGAA 933 GGTGGACAGGGCATGGATTCTTC 953 _human_776
ATTGCAAGTGAAGGAGCCTCCC 14 TNFSF4_NM_003326 GATGTCAAATAGCACTAAGA 934
TATCAAATTCAATCTGATGTCAAA 954 _human_1721 TAGCACTAAGAAGTTATTGTG 15
TNFSF4_NM_003326 GTATACAGGGAGAGTGAGAT 935 AAGAGAGATTTTCTTGTATACAG
955 _human_1459 GGAGAGTGAGATAACTTATTGT 16 TNFSF4_NM_003326
GTTGCTATGAGTCAAGGAGT 936 AATGTCTATGTTCTTGTTGCTATG 956 _human_3152
AGTCAAGGAGTGTAACCTTCT 17 TNFSF4_NM_003326 TAGTTGAAATGTCCCCTTAA 937
GTATCCCCTTATGTTTAGTTGAAA 957 _human_1882 TGTCCCCTTAACTTGATATAA 18
TNFSF4_NM_003326 CTCTGTGCCAAACCTTTTAT 938 GATGATTTGTAACTTCTCTGTGCC
958 _human_1980 AAACCTTTTATAAACATAAAT 19 TNFSF4_NM_003326
CTCTGTCTAGAAATACCATA 939 ATGAAAAATAATGATCTCTGTCTA 959 _human_1770
GAAATACCATAGACCATATAT 20 TNFSF4_NM_003326 GGTTTCAAGAAATGAGGTGA 940
CACAGAAACATTGCTGGTTTCAA 960 _human_1680 GAAATGAGGTGATCCTATTATC
Accession: NM_006293 HUGO gene symbol: TYRO3 1 TYRO3_NM_006293
AGTTGCTGTTTAAAATAGAA 961 CATTTCCAAGCTGTTAGTTGCTGTT 981 _human_3927
TAAAATAGAAATAAAATTGA 2 TYRO3_NM_006293 CTGTTTAAAATAGAAATAAA 962
CCAAGCTGTTAGTTGCTGTTTAAAA 982 _human_3932 TAGAAATAAAATTGAAGACT 3
TYRO3_NM_006293 GGCATCAGCGATGAACTAAA 963 ACATTGGACAGCTTGGGCATCAGC
983 _human_1731 GATGAACTAAAGGAAAAACTG 4 TYRO3_NM_006293
AATATCCTAAGACTAACAAA 964 GCTACCAAATCTCAAAATATCCTAA 984 _human_3699
GACTAACAAAGGCAGCTGTG 5 TYRO3_NM_006293 GTTGCTGTTTAAAATAGAAA 965
ATTTCCAAGCTGTTAGTTGCTGTTT 985 _human_3928 AAAATAGAAATAAAATTGAA 6
TYRO3_NM_006293 AAAATAGAAATAAAATTGAA 966 TGTTAGTTGCTGTTTAAAATAGAAA
986 _human_3938 TAAAATTGAAGACTAAAGAC 7 TYRO3_NM_006293
CTGTGAAGCTCACAACCTAA 967 GAGCACCATGTTTTCCTGTGAAGC 987 _human_842
TCACAACCTAAAAGGCCTGGC 8 TYRO3_NM_006293 TTGAAGACTAAAGACCTAAA 968
AAAATAGAAATAAAATTGAAGACT 988 _human_3953 AAAGACCTAAAAAAAAAAAAA 9
TYRO3_NM_006293 TCCTAAGACTAACAAAGGCA 969 CCAAATCTCAAAATATCCTAAGACT
989 _human_3703 AACAAAGGCAGCTGTGTCTG 10 TYRO3_NM_006293
GGACATTTCCAAGCTGTTAG 970 GGTCCTAGCTGTTAGGGACATTTC 990 _human_3909
CAAGCTGTTAGTTGCTGTTTA 11 TYRO3_NM_006293 ATGTTTCCATGGTTACCATG 971
AGGAGTGGGGTGGTTATGTTTCCA 991 _human_3190 TGGTTACCATGGGTGTGGATG 12
TYRO3_NM_006293 TAGTTGCTGTTTAAAATAGA 972 ACATTTCCAAGCTGTTAGTTGCTGT
992 _human_3926 TTAAAATAGAAATAAAATTG 13 TYRO3_NM_006293
AAAATTGAAGACTAAAGACC 973 GTTTAAAATAGAAATAAAATTGAA 993 _human_3949
GACTAAAGACCTAAAAAAAAA 14 TYRO3_NM_006293 AGCTGTTAGGGACATTTCCA 974
CATGGGGCGGGTCCTAGCTGTTAG 994 _human_3900 GGACATTTCCAAGCTGTTAGT 15
TYRO3_NM_006293 GAGGACGTGTATGATCTCAT 975 CCTCCGGAGTGTATGGAGGACGTG
995 _human_2511 TATGATCTCATGTACCAGTGC 16 TYRO3_NM_006293
TTTTAGGTGAGGGTTGGTAA 976 CCTTGTAATATTCCCTTTTAGGTGA 996 _human_3400
GGGTTGGTAAGGGGTTGGTA 17 TYRO3_NM_006293 AGCTGACATCATTGCCTCAA 977
TGTGAAGATGCTGAAAGCTGACAT 997 _human_1895 CATTGCCTCAAGCGACATTGA 18
TYRO3_NM_006293 AAATCTCAAAATATCCTAAG 978 TCTGAGCACGCTACCAAATCTCAA
998 _human_3690 AATATCCTAAGACTAACAAAG 19 TYRO3_NM_006293
AAGCTGTTAGTTGCTGTTTA 979 GTTAGGGACATTTCCAAGCTGTTA 999 _human_3919
GTTGCTGTTTAAAATAGAAAT 20 TYRO3_NM_006293 TCCTTGTAATATTCCCTTTT 980
AGTCACAAAGAGATGTCCTTGTAA 1000 _human_3384 TATTCCCTTTTAGGTGAGGGT
Accession: NM_000546 HUGO gene symbol: TP53 1 TP53_NM_000546_
TGTTTGGGAGATGTAAGAAA 81 TTTTACTGTGAGGGATGTTTGGG 101 human_1630
AGATGTAAGAAATGTTCTTGCA 2 TP53_NM_000546_ GCATTGTGAGGGTTAATGAA 82
CCTACCTCACAGAGTGCATTGTGA 102 human_1808 GGGTTAATGAAATAATGTACA 3
TP53_NM_000546_ TCGATCTCTTATTTTACAAT 83 TATCCCATTTTTATATCGATCTCTT
103 human_2538 ATTTTACAATAAAACTTTGC 4 TP53_NM_000546_
TGTGAGGGTTAATGAAATAA 84 CCTCACAGAGTGCATTGTGAGGG 104 human_1812
TTAATGAAATAATGTACATCTG 5 TP53_NM_000546_ GAGTATTTGGATGACAGAAA 85
GGAAATTTGCGTGTGGAGTATTT 105 human_812 GGATGACAGAAACACTTTTCGA 6
TP53_NM_000546_ GGATGTTTGGGAGATGTAAG 86 GGTTTTTACTGTGAGGGATGTTTG
106 human_1627 GGAGATGTAAGAAATGTTCTT 7 TP53_NM_000546_
GAAATGTTCTTGCAGTTAAG 87 GTTTGGGAGATGTAAGAAATGTT 107 human_1646
CTTGCAGTTAAGGGTTAGTTTA 8 TP53_NM_000546_ ATGTACATCTGGCCTTGAAA 88
AGGGTTAATGAAATAATGTACAT 108 human_1831 CTGGCCTTGAAACCACCTTTTA 9
TP53_NM_000546_ AGAAATGTTCTTGCAGTTAA 89 TGTTTGGGAGATGTAAGAAATGT 109
human_1645 TCTTGCAGTTAAGGGTTAGTTT 10 TP53_NM_000546_
GGTGAACCTTAGTACCTAAA 90 GTCTGACAACCTCTTGGTGAACCT 110 human_2015
TAGTACCTAAAAGGAAATCTC 11 TP53_NM_000546_ TAACTTCAAGGCCCATATCT 91
CTGTTGAATTTTCTCTAACTTCAA 111 human_1753 GGCCCATATCTGTGAAATGCT 12
TP53_NM_000546_ CTTATCCGAGTGGAAGGAAA 92 GCCCCTCCTCAGCATCTTATCCGA
112 human_782 GTGGAAGGAAATTTGCGTGTG 13 TP53_NM_000546_
ATGATCTGGATCCACCAAGA 93 CATCTCTTGTATATGATGATCTGG 113 human_2086
ATCCACCAAGACTTGTTTTAT 14 TP53_NM_000546_ AATTTTCTCTAACTTCAAGG 94
TGTCCCTCACTGTTGAATTTTCTCT 114 human_1744 AACTTCAAGGCCCATATCTG 15
TP53_NM_000546_ TCTCTTATTTTACAATAAAA 95 CCATTTTTATATCGATCTCTTATTT
115 human_2542 TACAATAAAACTTTGCTGCC 16 TP53_NM_000546_
TTATTTTACAATAAAACTTT 96 TTTTATATCGATCTCTTATTTTACA 116 human_2546
ATAAAACTTTGCTGCCACCT 17 TP53_NM_000546_ GCCTTGAAACCACCTTTTAT 97
AATAATGTACATCTGGCCTTGAAA 117 human_1842 CCACCTTTTATTACATGGGGT 18
TP53_NM_000546_ TATATCGATCTCTTATTTTA 98 TTTATATCCCATTTTTATATCGATC
118 human_2534 TCTTATTTTACAATAAAACT 19 TP53_NM_000546_
CCTTAGTACCTAAAAGGAAA 99 CAACCTCTTGGTGAACCTTAGTAC 119 human_2021
CTAAAAGGAAATCTCACCCCA 20 TP53_NM_000546_ CATTGTGAGGGTTAATGAAA 100
CTACCTCACAGAGTGCATTGTGA 120 human_1809 GGGTTAATGAAATAATGTACAT
Sequence CWU 1
1
1007120DNAHomo sapiens 1gaattgctca agttcattga 20220DNAHomo sapiens
2ttcatccagg atcgagcagg 20320DNAHomo sapiens 3atcatcagat gtggtctata
20420DNAHomo sapiens 4tactttgcca gcaaactggt 20520DNAHomo sapiens
5ggttgggtga gactcctcaa 20620DNAHomo sapiens 6ctactttgcc agcaaactgg
20720DNAHomo sapiens 7gcgttttcct tacgtgtctg 20820DNAHomo sapiens
8tacgtgtctg atcaatcccc 20920DNAHomo sapiens 9tcagggtttc atccaggatc
201020DNAHomo sapiens 10tgacggcaac ttcaactggg 201120DNAHomo sapiens
11cagctgacat gttttctgac 201220DNAHomo sapiens 12agctgacatg
ttttctgacg 201320DNAHomo sapiens 13cactgtgacc ttgacttgat
201420DNAHomo sapiens 14tccttacgtg tctgatcaat 201520DNAHomo sapiens
15gatcagaacc atcatgggct 201620DNAHomo sapiens 16cttctggagc
aggtcacagt 201720DNAHomo sapiens 17tgagcagatc atgaagacag
201820DNAHomo sapiens 18tataatgcgt tttccttacg 201920DNAHomo sapiens
19cccatcttca gatcatcaga 202020DNAHomo sapiens 20aggtgccgga
actgatcaga 202145DNAHomo sapiens 21cctccactgc ctctggaatt gctcaagttc
attgatgacc ctctg 452245DNAHomo sapiens 22cttttgcttc agggtttcat
ccaggatcga gcagggcgaa tgggg 452345DNAHomo sapiens 23tctccccatc
ttcagatcat cagatgtggt ctataatgcg ttttc 452445DNAHomo sapiens
24gttgtcgccc ttttctactt tgccagcaaa ctggtgctca aggcc 452545DNAHomo
sapiens 25atccaagacc agggtggttg ggtgagactc ctcaagcctc ctcac
452645DNAHomo sapiens 26ggttgtcgcc cttttctact ttgccagcaa actggtgctc
aaggc 452745DNAHomo sapiens 27gatgtggtct ataatgcgtt ttccttacgt
gtctgatcaa tcccc 452845DNAHomo sapiens 28ataatgcgtt ttccttacgt
gtctgatcaa tccccgattc atcta 452945DNAHomo sapiens 29aggggccctt
ttgcttcagg gtttcatcca ggatcgagca gggcg 453045DNAHomo sapiens
30agctgacatg ttttctgacg gcaacttcaa ctggggccgg gttgt 453145DNAHomo
sapiens 31tctttttccg agtggcagct gacatgtttt ctgacggcaa cttca
453245DNAHomo sapiens 32ctttttccga gtggcagctg acatgttttc tgacggcaac
ttcaa 453345DNAHomo sapiens 33agtgacccct gacctcactg tgaccttgac
ttgattagtg ccttc 453445DNAHomo sapiens 34gtctataatg cgttttcctt
acgtgtctga tcaatccccg attca 453545DNAHomo sapiens 35caaggtgccg
gaactgatca gaaccatcat gggctggaca ttgga 453645DNAHomo sapiens
36tctgggaccc tgggccttct ggagcaggtc acagtggtgc cctct 453745DNAHomo
sapiens 37ggggcccacc agctctgagc agatcatgaa gacaggggcc ctttt
453845DNAHomo sapiens 38tcatcagatg tggtctataa tgcgttttcc ttacgtgtct
gatca 453945DNAHomo sapiens 39cagtggtgcc ctctccccat cttcagatca
tcagatgtgg tctat 454045DNAHomo sapiens 40aggccctgtg caccaaggtg
ccggaactga tcagaaccat catgg 454120DNAHomo sapiens 41tggtttgtta
tatcagggaa 204220DNAHomo sapiens 42tggtacgaag attcttcaaa
204320DNAHomo sapiens 43ttatatcagg gaaaaggagt 204420DNAHomo sapiens
44tcccttcctc tctccttata 204520DNAHomo sapiens 45tcaaatcatg
actcccaagg 204620DNAHomo sapiens 46tgttatatca gggaaaagga
204720DNAHomo sapiens 47acgaagattc ttcaaatcat 204820DNAHomo sapiens
48ggtacgaaga ttcttcaaat 204920DNAHomo sapiens 49gaagttcttg
attcagccaa 205020DNAHomo sapiens 50cctatgagta cttcaccaag
205120DNAHomo sapiens 51tatcagggaa aaggagtagg 205220DNAHomo sapiens
52ctctccttat agacacttgc 205320DNAHomo sapiens 53acttggtttg
ttatatcagg 205420DNAHomo sapiens 54aagatcagca ccctaagaga
205520DNAHomo sapiens 55gtttgagagt ggcatcaatt 205620DNAHomo sapiens
56gactatcaac accactagga 205720DNAHomo sapiens 57agctttagca
agtgtgcact 205820DNAHomo sapiens 58ttcatctgga gggttctaag
205920DNAHomo sapiens 59aagttcttga ttcagccaaa 206020DNAHomo sapiens
60gttatatcag ggaaaaggag 206145DNAHomo sapiens 61acagggctta
ggacttggtt tgttatatca gggaaaagga gtagg 456245DNAHomo sapiens
62tgttgggcca gtttgtggta cgaagattct tcaaatcatg actcc 456345DNAHomo
sapiens 63ttaggacttg gtttgttata tcagggaaaa ggagtaggga gttca
456445DNAHomo sapiens 64gtcctctcag ttctctccct tcctctctcc ttatagacac
ttgct 456545DNAHomo sapiens 65tggtacgaag attcttcaaa tcatgactcc
caagggtgcc ctttg 456645DNAHomo sapiens 66gcttaggact tggtttgtta
tatcagggaa aaggagtagg gagtt 456745DNAHomo sapiens 67gggccagttt
gtggtacgaa gattcttcaa atcatgactc ccaag 456845DNAHomo sapiens
68gttgggccag tttgtggtac gaagattctt caaatcatga ctccc 456945DNAHomo
sapiens 69gggggtcagg ggggagaagt tcttgattca gccaaatgca gggag
457045DNAHomo sapiens 70ccacggcaga gaatgcctat gagtacttca ccaagattgc
cacca 457145DNAHomo sapiens 71ggacttggtt tgttatatca gggaaaagga
gtagggagtt catct 457245DNAHomo sapiens 72gttctctccc ttcctctctc
cttatagaca cttgctccca accca 457345DNAHomo sapiens 73actacagggc
ttaggacttg gtttgttata tcagggaaaa ggagt 457445DNAHomo sapiens
74attcagctat tctggaagat cagcacccta agagatggga ctagg 457545DNAHomo
sapiens 75gattgccacc agcctgtttg agagtggcat caattggggc cgtgt
457645DNAHomo sapiens 76tctaagtggg agaaggacta tcaacaccac taggaatccc
agagg 457745DNAHomo sapiens 77cctcaagagt acagaagctt tagcaagtgt
gcactccagc ttcgg 457845DNAHomo sapiens 78aaaaggagta gggagttcat
ctggagggtt ctaagtggga gaagg 457945DNAHomo sapiens 79ggggtcaggg
gggagaagtt cttgattcag ccaaatgcag ggagg 458045DNAHomo sapiens
80cttaggactt ggtttgttat atcagggaaa aggagtaggg agttc 458120DNAHomo
sapiens 81tgtttgggag atgtaagaaa 208220DNAHomo sapiens 82gcattgtgag
ggttaatgaa 208320DNAHomo sapiens 83tcgatctctt attttacaat
208420DNAHomo sapiens 84tgtgagggtt aatgaaataa 208520DNAHomo sapiens
85gagtatttgg atgacagaaa 208620DNAHomo sapiens 86ggatgtttgg
gagatgtaag 208720DNAHomo sapiens 87gaaatgttct tgcagttaag
208820DNAHomo sapiens 88atgtacatct ggccttgaaa 208920DNAHomo sapiens
89agaaatgttc ttgcagttaa 209020DNAHomo sapiens 90ggtgaacctt
agtacctaaa 209120DNAHomo sapiens 91taacttcaag gcccatatct
209220DNAHomo sapiens 92cttatccgag tggaaggaaa 209320DNAHomo sapiens
93atgatctgga tccaccaaga 209420DNAHomo sapiens 94aattttctct
aacttcaagg 209520DNAHomo sapiens 95tctcttattt tacaataaaa
209620DNAHomo sapiens 96ttattttaca ataaaacttt 209720DNAHomo sapiens
97gccttgaaac caccttttat 209820DNAHomo sapiens 98tatatcgatc
tcttatttta 209920DNAHomo sapiens 99ccttagtacc taaaaggaaa
2010020DNAHomo sapiens 100cattgtgagg gttaatgaaa 2010145DNAHomo
sapiens 101ttttactgtg agggatgttt gggagatgta agaaatgttc ttgca
4510245DNAHomo sapiens 102cctacctcac agagtgcatt gtgagggtta
atgaaataat gtaca 4510345DNAHomo sapiens 103tatcccattt ttatatcgat
ctcttatttt acaataaaac tttgc 4510445DNAHomo sapiens 104cctcacagag
tgcattgtga gggttaatga aataatgtac atctg 4510545DNAHomo sapiens
105ggaaatttgc gtgtggagta tttggatgac agaaacactt ttcga 4510645DNAHomo
sapiens 106ggtttttact gtgagggatg tttgggagat gtaagaaatg ttctt
4510745DNAHomo sapiens 107gtttgggaga tgtaagaaat gttcttgcag
ttaagggtta gttta 4510845DNAHomo sapiens 108agggttaatg aaataatgta
catctggcct tgaaaccacc tttta 4510945DNAHomo sapiens 109tgtttgggag
atgtaagaaa tgttcttgca gttaagggtt agttt 4511045DNAHomo sapiens
110gtctgacaac ctcttggtga accttagtac ctaaaaggaa atctc 4511145DNAHomo
sapiens 111ctgttgaatt ttctctaact tcaaggccca tatctgtgaa atgct
4511245DNAHomo sapiens 112gcccctcctc agcatcttat ccgagtggaa
ggaaatttgc gtgtg 4511345DNAHomo sapiens 113catctcttgt atatgatgat
ctggatccac caagacttgt tttat 4511445DNAHomo sapiens 114tgtccctcac
tgttgaattt tctctaactt caaggcccat atctg 4511545DNAHomo sapiens
115ccatttttat atcgatctct tattttacaa taaaactttg ctgcc 4511645DNAHomo
sapiens 116ttttatatcg atctcttatt ttacaataaa actttgctgc cacct
4511745DNAHomo sapiens 117aataatgtac atctggcctt gaaaccacct
tttattacat ggggt 4511845DNAHomo sapiens 118tttatatccc atttttatat
cgatctctta ttttacaata aaact 4511945DNAHomo sapiens 119caacctcttg
gtgaacctta gtacctaaaa ggaaatctca cccca 4512045DNAHomo sapiens
120ctacctcaca gagtgcattg tgagggttaa tgaaataatg tacat 4512120DNAHomo
sapiens 121ttaaatcatt aggaattaag 2012220DNAHomo sapiens
122gaattaagtt atctttaaaa 2012320DNAHomo sapiens 123aactttaatt
ctctttcaaa 2012420DNAHomo sapiens 124gactgaagtg aactatgaag
2012520DNAHomo sapiens 125atattctcct gccttttaaa 2012620DNAHomo
sapiens 126agttatcttt aaaatttaag 2012720DNAHomo sapiens
127tagattttct actttattaa 2012820DNAHomo sapiens 128ctgtgcccaa
atcaacaaga 2012920DNAHomo sapiens 129agctggtggc aataaatacc
2013020DNAHomo sapiens 130tcctaccgaa accctgcaga 2013120DNAHomo
sapiens 131tataagagct aaagttaaat 2013220DNAHomo sapiens
132cactatgttt atttactaat 2013320DNAHomo sapiens 133attgttatct
atcaactata 2013420DNAHomo sapiens 134taactgtgtt tcctaccgaa
2013520DNAHomo sapiens 135taattctctt tcaaagctaa 2013620DNAHomo
sapiens 136tatatgcttg gctaactata 2013720DNAHomo sapiens
137ctctgcttgg attattttaa 2013820DNAHomo sapiens 138atgcttggct
aactatattt 2013920DNAHomo sapiens 139ataagagcta aagttaaata
2014020DNAHomo sapiens 140atctttaaaa tttaagtatc 2014145DNAHomo
sapiens 141tctgcttgga ttattttaaa tcattaggaa ttaagttatc tttaa
4514245DNAHomo sapiens 142attttaaatc attaggaatt aagttatctt
taaaatttaa gtatc 4514345DNAHomo sapiens 143tgttaatatt ctattaactt
taattctctt tcaaagctaa attcc 4514445DNAHomo sapiens 144tattctcacc
atcctgactg aagtgaacta tgaagtaagc aacaa 4514545DNAHomo sapiens
145gggaatattg agattatatt ctcctgcctt ttaaaaagat ggact 4514645DNAHomo
sapiens 146aatcattagg aattaagtta tctttaaaat ttaagtatct ttttt
4514745DNAHomo sapiens 147tatttactaa ttttctagat tttctacttt
attaattgtt ttgca 4514845DNAHomo sapiens 148catcctgaaa agagtctgtg
cccaaatcaa caagagcctg ctgaa 4514945DNAHomo sapiens 149tttgggaatg
tttttagctg gtggcaataa ataccagaca cgtac 4515045DNAHomo sapiens
150gtgaataact gtgtttccta ccgaaaccct gcagagggaa cctgg 4515145DNAHomo
sapiens 151tgttttgcac ttttttataa gagctaaagt taaataggat attaa
4515245DNAHomo sapiens 152actatttaga tataacacta tgtttattta
ctaattttct agatt 4515345DNAHomo sapiens 153gggcttatga ttcagattgt
tatctatcaa ctataagccc actgt 4515445DNAHomo sapiens 154gatggccact
gtgaataact gtgtttccta ccgaaaccct gcaga 4515545DNAHomo sapiens
155atattctatt aactttaatt ctctttcaaa gctaaattcc acact 4515645DNAHomo
sapiens 156tgcttttatg atatatatat gcttggctaa ctatatttgc ttttt
4515745DNAHomo sapiens 157catttgctct ttcatctctg cttggattat
tttaaatcat tagga 4515845DNAHomo sapiens 158ttttatgata tatatatgct
tggctaacta tatttgcttt ttgct 4515945DNAHomo sapiens 159gttttgcact
tttttataag agctaaagtt aaataggata ttaac 4516045DNAHomo sapiens
160attaggaatt aagttatctt taaaatttaa gtatcttttt tcaaa 4516120DNAHomo
sapiens 161taactgcctt tccttctaaa 2016220DNAHomo sapiens
162ttccttctaa agggaatgtt 2016320DNAHomo sapiens 163gcctttcctt
ctaaagggaa 2016420DNAHomo sapiens 164ttttctgaga taaaataaaa
2016520DNAHomo sapiens 165catctcttgg agtgacaaag 2016620DNAHomo
sapiens 166catggtgtac ttcaacttct 2016720DNAHomo sapiens
167ctaactgcct ttccttctaa 2016820DNAHomo sapiens 168ctgatgattc
atggagtttg 2016920DNAHomo sapiens 169ctcagagtcc tctgtgaaaa
2017020DNAHomo sapiens 170aacgagccac atcgtgtttt 2017120DNAHomo
sapiens 171tccttctaaa gggaatgttt 2017220DNAHomo sapiens
172catgaactac atggtgtact 2017320DNAHomo sapiens 173aactgccttt
ccttctaaag 2017420DNAHomo sapiens 174cagatgtttc atgctgtgag
2017520DNAHomo sapiens 175cccatgaact acatggtgta 2017620DNAHomo
sapiens 176aggcagcaag aacctttcaa 2017720DNAHomo sapiens
177gtcctgatga ttcatggagt 2017820DNAHomo sapiens 178gtacttcaac
ttctttgcct 2017920DNAHomo sapiens 179tgtaagtgtg aggaaaccct
2018020DNAHomo sapiens 180cctactttgg actgagagaa 2018145DNAHomo
sapiens 181gtgagaggcc ttgtctaact gcctttcctt ctaaagggaa tgttt
4518245DNAHomo sapiens 182cttgtctaac tgcctttcct tctaaaggga
atgttttttt ctgag 4518345DNAHomo sapiens 183aggccttgtc taactgcctt
tccttctaaa gggaatgttt ttttc 4518445DNAHomo sapiens 184ctaaagggaa
tgtttttttc tgagataaaa taaaaacgag ccaca 4518545DNAHomo sapiens
185tctcagtccc agggccatct cttggagtga caaagctggg atcaa 4518645DNAHomo
sapiens 186ggtccccatg aactacatgg tgtacttcaa cttctttgcc tgtgt
4518745DNAHomo sapiens 187agtgagaggc cttgtctaac tgcctttcct
tctaaaggga atgtt 4518845DNAHomo sapiens 188tggagcagga gtgtcctgat
gattcatgga gtttgcccct tccta 4518945DNAHomo sapiens 189cctggtttca
ggagactcag agtcctctgt gaaaaagccc
ttgga 4519045DNAHomo sapiens 190ctgagataaa ataaaaacga gccacatcgt
gttttaagct tgtcc 4519145DNAHomo sapiens 191ttgtctaact gcctttcctt
ctaaagggaa tgtttttttc tgaga 4519245DNAHomo sapiens 192tgaggatgtg
gtccccatga actacatggt gtacttcaac ttctt 4519345DNAHomo sapiens
193tgagaggcct tgtctaactg cctttccttc taaagggaat gtttt 4519445DNAHomo
sapiens 194tgggttctga ggaagcagat gtttcatgct gtgaggcctt gcacc
4519545DNAHomo sapiens 195tttgaggatg tggtccccat gaactacatg
gtgtacttca acttc 4519645DNAHomo sapiens 196cgcagccacg tcctgaggca
gcaagaacct ttcaaggcag ctggc 4519745DNAHomo sapiens 197ggatggagca
ggagtgtcct gatgattcat ggagtttgcc ccttc 4519845DNAHomo sapiens
198catgaactac atggtgtact tcaacttctt tgcctgtgtg ctggt 4519945DNAHomo
sapiens 199tttttccagg aaaaatgtaa gtgtgaggaa acccttttta tttta
4520045DNAHomo sapiens 200tgagggcagc cggttcctac tttggactga
gagaagggag cccca 4520120DNAHomo sapiens 201tgattctgtg tgggttcaaa
2020220DNAHomo sapiens 202ttatttgttt gtgcatttgg 2020320DNAHomo
sapiens 203tgattacatc aaggcttcaa 2020420DNAHomo sapiens
204gatgtgggtc aaggaattaa 2020520DNAHomo sapiens 205ccttttattt
cttaaacaaa 2020620DNAHomo sapiens 206gattacatca aggcttcaaa
2020720DNAHomo sapiens 207tctgtgtggg ttcaaacaca 2020820DNAHomo
sapiens 208ttgatagtat tgtgcataga 2020920DNAHomo sapiens
209tgccttttat ttcttaaaca 2021020DNAHomo sapiens 210tccatgaaaa
tgcaacaaca 2021120DNAHomo sapiens 211ttatttctta aacaaatgta
2021220DNAHomo sapiens 212ttaatggttt gaatataaac 2021320DNAHomo
sapiens 213atgtgggtca aggaattaag 2021420DNAHomo sapiens
214agccgaaatg atcttttcaa 2021520DNAHomo sapiens 215gtttgaatat
aaacactata 2021620DNAHomo sapiens 216tatgcctttt atttcttaaa
2021720DNAHomo sapiens 217ttccatgaaa atgcaacaac 2021820DNAHomo
sapiens 218catctctctt taatataaag 2021920DNAHomo sapiens
219ggaattcatc tctctttaat 2022020DNAHomo sapiens 220atctatataa
agtccttgat 2022145DNAHomo sapiens 221tctatataaa gtccttgatt
ctgtgtgggt tcaaacacat ttcaa 4522245DNAHomo sapiens 222gctatccagc
tatttttatt tgtttgtgca tttgggggga attca 4522345DNAHomo sapiens
223tcttaaacaa atgtatgatt acatcaaggc ttcaaaaata ctcac 4522445DNAHomo
sapiens 224gggatgcagc attatgatgt gggtcaagga attaagttag ggaat
4522545DNAHomo sapiens 225aagttaaatt ttatgccttt tatttcttaa
acaaatgtat gatta 4522645DNAHomo sapiens 226cttaaacaaa tgtatgatta
catcaaggct tcaaaaatac tcaca 4522745DNAHomo sapiens 227tataaagtcc
ttgattctgt gtgggttcaa acacatttca aagct 4522845DNAHomo sapiens
228tatatatatt ttaatttgat agtattgtgc atagagccac gtatg 4522945DNAHomo
sapiens 229tcaagttaaa ttttatgcct tttatttctt aaacaaatgt atgat
4523045DNAHomo sapiens 230tttaactcaa tattttccat gaaaatgcaa
caacatgtat aatat 4523145DNAHomo sapiens 231taaattttat gccttttatt
tcttaaacaa atgtatgatt acatc 4523245DNAHomo sapiens 232gtttttgtgt
atttgttaat ggtttgaata taaacactat atggc 4523345DNAHomo sapiens
233ggatgcagca ttatgatgtg ggtcaaggaa ttaagttagg gaatg 4523445DNAHomo
sapiens 234gtatgagacg tttatagccg aaatgatctt ttcaagttaa atttt
4523545DNAHomo sapiens 235gtgtatttgt taatggtttg aatataaaca
ctatatggca gtgtc 4523645DNAHomo sapiens 236tttcaagtta aattttatgc
cttttatttc ttaaacaaat gtatg 4523745DNAHomo sapiens 237ttttaactca
atattttcca tgaaaatgca acaacatgta taata 4523845DNAHomo sapiens
238catttggggg gaattcatct ctctttaata taaagttgga tgcgg 4523945DNAHomo
sapiens 239tttgtgcatt tggggggaat tcatctctct ttaatataaa gttgg
4524045DNAHomo sapiens 240tctgggatca aagctatcta tataaagtcc
ttgattctgt gtggg 4524120DNAHomo sapiens 241gactttaccc ttcgactaga
2024220DNAHomo sapiens 242caacgtctcc atcatgtata 2024320DNAHomo
sapiens 243gtcctttctc tgctcctttt 2024420DNAHomo sapiens
244tccagtatct ggacaagaac 2024520DNAHomo sapiens 245attttctgcc
ttagagcaag 2024620DNAHomo sapiens 246tttcaccttt ggagaagaca
2024720DNAHomo sapiens 247cattttgaac tgctccttca 2024820DNAHomo
sapiens 248tcatcacagt gactcccaaa 2024920DNAHomo sapiens
249gctttcacct ttggagaaga 2025020DNAHomo sapiens 250ctttggcttt
cacctttgga 2025120DNAHomo sapiens 251attttgaact gctccttcag
2025220DNAHomo sapiens 252cacattggca atcatcacag 2025320DNAHomo
sapiens 253tttctgacct ccttttggag 2025420DNAHomo sapiens
254cgactgggtc attttgaact 2025520DNAHomo sapiens 255tacttcacag
agctgtctag 2025620DNAHomo sapiens 256attggcaatc atcacagtga
2025720DNAHomo sapiens 257ctgtttctca tccttggtgt 2025820DNAHomo
sapiens 258ttgtgaggtg actccagtat 2025920DNAHomo sapiens
259tttggctttc acctttggag 2026020DNAHomo sapiens 260tggagacaat
ggcgacttta 2026145DNAHomo sapiens 261actggagaca atggcgactt
tacccttcga ctagaggatg tgagc 4526245DNAHomo sapiens 262ctacagagat
ggcttcaacg tctccatcat gtataacctc actgt 4526345DNAHomo sapiens
263tttctcatcc ttggtgtcct ttctctgctc cttttggtga ctgga 4526445DNAHomo
sapiens 264gctttgtgag gtgactccag tatctggaca agaacgcttt gtgtg
4526545DNAHomo sapiens 265gtggcgacca agacgatttt ctgccttaga
gcaagggatt caccc 4526645DNAHomo sapiens 266actggagcct ttggctttca
cctttggaga agacagtggc gacca 4526745DNAHomo sapiens 267agcctccgac
tgggtcattt tgaactgctc cttcagccgc cctga 4526845DNAHomo sapiens
268ctgtcacatt ggcaatcatc acagtgactc ccaaatcctt tgggt 4526945DNAHomo
sapiens 269tgactggagc ctttggcttt cacctttgga gaagacagtg gcgac
4527045DNAHomo sapiens 270tttggtgact ggagcctttg gctttcacct
ttggagaaga cagtg 4527145DNAHomo sapiens 271gcctccgact gggtcatttt
gaactgctcc ttcagccgcc ctgac 4527245DNAHomo sapiens 272gctcaatgcc
actgtcacat tggcaatcat cacagtgact cccaa 4527345DNAHomo sapiens
273actgccccct ttccttttct gacctccttt tggagggctc agcgc 4527445DNAHomo
sapiens 274atctctcaga gcctccgact gggtcatttt gaactgctcc ttcag
4527545DNAHomo sapiens 275cttggagcag cagtgtactt cacagagctg
tctagcccag gtgcc 4527645DNAHomo sapiens 276caatgccact gtcacattgg
caatcatcac agtgactccc aaatc 4527745DNAHomo sapiens 277gcaggccacc
tcctgctgtt tctcatcctt ggtgtccttt ctctg 4527845DNAHomo sapiens
278cctggggaag ctgctttgtg aggtgactcc agtatctgga caaga 4527945DNAHomo
sapiens 279ttggtgactg gagcctttgg ctttcacctt tggagaagac agtgg
4528045DNAHomo sapiens 280tgacctcctg gtgactggag acaatggcga
ctttaccctt cgact 4528120DNAHomo sapiens 281tattatatta taattataat
2028220DNAHomo sapiens 282tctattatat tataattata 2028320DNAHomo
sapiens 283cattcctgaa attatttaaa 2028420DNAHomo sapiens
284ctattatatt ataattataa 2028520DNAHomo sapiens 285agtttcaggg
aaggtcagaa 2028620DNAHomo sapiens 286tgtggttcta ttatattata
2028720DNAHomo sapiens 287tgtgttctct gtggactatg 2028820DNAHomo
sapiens 288cccattcctg aaattattta 2028920DNAHomo sapiens
289tgccaccatt gtctttccta 2029020DNAHomo sapiens 290aagtttcagg
gaaggtcaga 2029120DNAHomo sapiens 291ctgtggttct attatattat
2029220DNAHomo sapiens 292ttctattata ttataattat 2029320DNAHomo
sapiens 293tttcagggaa ggtcagaaga 2029420DNAHomo sapiens
294cttggaaccc attcctgaaa 2029520DNAHomo sapiens 295tccctgtggt
tctattatat 2029620DNAHomo sapiens 296cctgtggttc tattatatta
2029720DNAHomo sapiens 297tggaacccat tcctgaaatt 2029820DNAHomo
sapiens 298ccttccctgt ggttctatta 2029920DNAHomo sapiens
299ttccctgtgg ttctattata 2030020DNAHomo sapiens 300cacaggactc
atgtctcaat 2030145DNAHomo sapiens 301ccttccctgt ggttctatta
tattataatt ataattaaat atgag 4530245DNAHomo sapiens 302ccccttccct
gtggttctat tatattataa ttataattaa atatg 4530345DNAHomo sapiens
303gctctccttg gaacccattc ctgaaattat ttaaaggggt tggcc 4530445DNAHomo
sapiens 304cccttccctg tggttctatt atattataat tataattaaa tatga
4530545DNAHomo sapiens 305ctgcaggcct agagaagttt cagggaaggt
cagaagagct cctgg 4530645DNAHomo sapiens 306gggatccccc ttccctgtgg
ttctattata ttataattat aatta 4530745DNAHomo sapiens 307cccctcagcc
gtgcctgtgt tctctgtgga ctatggggag ctgga 4530845DNAHomo sapiens
308gagctctcct tggaacccat tcctgaaatt atttaaaggg gttgg 4530945DNAHomo
sapiens 309tgagcagacg gagtatgcca ccattgtctt tcctagcgga atggg
4531045DNAHomo sapiens 310cctgcaggcc tagagaagtt tcagggaagg
tcagaagagc tcctg 4531145DNAHomo sapiens 311agggatcccc cttccctgtg
gttctattat attataatta taatt 4531245DNAHomo sapiens 312cccccttccc
tgtggttcta ttatattata attataatta aatat 4531345DNAHomo sapiens
313gcaggcctag agaagtttca gggaaggtca gaagagctcc tggct 4531445DNAHomo
sapiens 314accctgggag ctctccttgg aacccattcc tgaaattatt taaag
4531545DNAHomo sapiens 315acaagggatc ccccttccct gtggttctat
tatattataa ttata 4531645DNAHomo sapiens 316aagggatccc ccttccctgt
ggttctatta tattataatt ataat 4531745DNAHomo sapiens 317cctgggagct
ctccttggaa cccattcctg aaattattta aaggg 4531845DNAHomo sapiens
318gggacaaggg atcccccttc cctgtggttc tattatatta taatt 4531945DNAHomo
sapiens 319gacaagggat cccccttccc tgtggttcta ttatattata attat
4532045DNAHomo sapiens 320caggcacagc cccaccacag gactcatgtc
tcaatgccca cagtg 4532120DNAHomo sapiens 321cctgtttatt acaacttaaa
2032220DNAHomo sapiens 322ccattggtgg aattcatgaa 2032320DNAHomo
sapiens 323ttttccttat aacaaagaca 2032420DNAHomo sapiens
324tgtattactt gtttaataat 2032520DNAHomo sapiens 325ttattgaatc
aaagattgag 2032620DNAHomo sapiens 326ttcttaccta agtggataaa
2032720DNAHomo sapiens 327atgttgctca gttactcaaa 2032820DNAHomo
sapiens 328atatttgtac cccaaataac 2032920DNAHomo sapiens
329tgtaaatgta aacttctaaa 2033020DNAHomo sapiens 330agaatgagtg
acatattaca 2033120DNAHomo sapiens 331ccatttctaa gcctaccaga
2033220DNAHomo sapiens 332atattccaaa agaatgtaaa 2033320DNAHomo
sapiens 333ttacttccaa tgctatgaag 2033420DNAHomo sapiens
334tctttatctg ttcaaagact 2033520DNAHomo sapiens 335gtctaagtat
acttttaaaa 2033620DNAHomo sapiens 336atctttggac atgtactgca
2033720DNAHomo sapiens 337gtgttgtatt acttgtttaa 2033820DNAHomo
sapiens 338tgctgtagat ggcaactaga 2033920DNAHomo sapiens
339tctttcactt attcagaaca 2034020DNAHomo sapiens 340gtatttgtag
taatattcca 2034145DNAHomo sapiens 341gttaataaca ttcaacctgt
ttattacaac ttaaaaggaa cttca 4534245DNAHomo sapiens 342ttgctcgacg
atgttccatt ggtggaattc atgaagatta ccaac 4534345DNAHomo sapiens
343tttagggatt tttttttttc cttataacaa agacatcacc aggat 4534445DNAHomo
sapiens 344tttttatagt tgtgttgtat tacttgttta ataataatct ctaat
4534545DNAHomo sapiens 345tgctgaagat attttttatt gaatcaaaga
ttgagttaca attat 4534645DNAHomo sapiens 346gttacaatta tacttttctt
acctaagtgg ataaaatgta ctttt 4534745DNAHomo sapiens 347taaagtatgg
gtattatgtt gctcagttac tcaaatggta ctgta 4534845DNAHomo sapiens
348ggtactgtat tgtttatatt tgtaccccaa ataacatcgt ctgta 4534945DNAHomo
sapiens 349ttatgcaatc ttgtttgtaa atgtaaactt ctaaaaatat ggtta
4535045DNAHomo sapiens 350aaccaaagta attttagaat gagtgacata
ttacatagga attta 4535145DNAHomo sapiens 351gttgttgttt ttgggccatt
tctaagccta ccagatctgc tttat 4535245DNAHomo sapiens 352attgtatttg
tagtaatatt ccaaaagaat gtaaatagga aatag 4535345DNAHomo sapiens
353tataataact ggtttttact tccaatgcta tgaagtctct gcagg 4535445DNAHomo
sapiens 354tgtaagccat ttttttcttt atctgttcaa agacttattt tttaa
4535545DNAHomo sapiens 355cattttaatt gtgttgtcta agtatacttt
taaaaaatca agtgg 4535645DNAHomo sapiens 356gagatactaa ggattatctt
tggacatgta ctgcagcttc ttgtc 4535745DNAHomo sapiens 357tttgttttta
tagttgtgtt gtattacttg tttaataata atctc 4535845DNAHomo sapiens
358catgccatat gtagttgctg tagatggcaa ctagaacctt tgagt 4535945DNAHomo
sapiens 359gtatactatt attgttcttt cacttattca gaacattaca tgcct
4536045DNAHomo sapiens 360tttaaattgt atattgtatt tgtagtaata
ttccaaaaga atgta 4536120DNAHomo sapiens 361ctcatagcaa agagaagata
2036220DNAHomo sapiens 362gtattctcat agcaaagaga 2036320DNAHomo
sapiens 363ttgcttgttg tgtgcttgaa 2036420DNAHomo sapiens
364tattcgtgga ccaaactgaa 2036520DNAHomo sapiens 365attgtggagt
agacagttgg 2036620DNAHomo sapiens 366gttgtgtgct tgaaagaaaa
2036720DNAHomo sapiens 367tgttgtgtgc ttgaaagaaa 2036820DNAHomo
sapiens 368ccctaaactt aaatttcaag 2036920DNAHomo sapiens
369acatccagat actggctaaa 2037020DNAHomo sapiens 370cattttcaga
agataatgac 2037120DNAHomo sapiens 371cacattggcc aatgagttac
2037220DNAHomo sapiens 372tgcttgttgt gtgcttgaaa 2037320DNAHomo
sapiens 373gagtagacag ttggaagaag 2037420DNAHomo sapiens
374ttgttgtgtg cttgaaagaa 2037520DNAHomo sapiens 375cggcgcttta
attttcaaat 2037620DNAHomo sapiens 376tttggcacag aaagtctaaa
2037720DNAHomo sapiens 377gatctgtctt gcttattgtt
2037820DNAHomo sapiens 378ggtgtgtatt ggccaagttt 2037920DNAHomo
sapiens 379cccattttca gaagataatg 2038020DNAHomo sapiens
380tggcacagaa agtctaaagg 2038145DNAHomo sapiens 381ttttcaaatg
gtattctcat agcaaagaga agatacagaa tttaa 4538245DNAHomo sapiens
382tttaattttc aaatggtatt ctcatagcaa agagaagata cagaa 4538345DNAHomo
sapiens 383tgtattggcc aagttttgct tgttgtgtgc ttgaaagaaa atatc
4538445DNAHomo sapiens 384tctgaccaac ttctgtattc gtggaccaaa
ctgaagctat atttt 4538545DNAHomo sapiens 385gctactgctc atgtgattgt
ggagtagaca gttggaagaa gtacc 4538645DNAHomo sapiens 386ggccaagttt
tgcttgttgt gtgcttgaaa gaaaatatct ctgac 4538745DNAHomo sapiens
387tggccaagtt ttgcttgttg tgtgcttgaa agaaaatatc tctga 4538845DNAHomo
sapiens 388ttgacagaga gtggtcccta aacttaaatt tcaagacggt atagg
4538945DNAHomo sapiens 389gatgtgaatt attggacatc cagatactgg
ctaaatgggg atttc 4539045DNAHomo sapiens 390ggagcagagt tttcccattt
tcagaagata atgactcaca tggga 4539145DNAHomo sapiens 391tctaacacaa
atatccacat tggccaatga gttacgggac tctag 4539245DNAHomo sapiens
392gtattggcca agttttgctt gttgtgtgct tgaaagaaaa tatct 4539345DNAHomo
sapiens 393gctcatgtga ttgtggagta gacagttgga agaagtaccc agtcc
4539445DNAHomo sapiens 394ttggccaagt tttgcttgtt gtgtgcttga
aagaaaatat ctctg 4539545DNAHomo sapiens 395tctggctctt atcttcggcg
ctttaatttt caaatggtat tctca 4539645DNAHomo sapiens 396tgaaagcata
acttttttgg cacagaaagt ctaaaggggc cactg 4539745DNAHomo sapiens
397agacggtata ggcttgatct gtcttgctta ttgttgcccc ctgcg 4539845DNAHomo
sapiens 398gaagtgcatt tgattggtgt gtattggcca agttttgctt gttgt
4539945DNAHomo sapiens 399atggagcaga gttttcccat tttcagaaga
taatgactca catgg 4540045DNAHomo sapiens 400aaagcataac ttttttggca
cagaaagtct aaaggggcca ctgat 4540120DNAHomo sapiens 401aaatacctgc
aaagccttga 2040220DNAHomo sapiens 402ttttgtaact gtgcagggca
2040320DNAHomo sapiens 403agagtgaaga atgcagttaa 2040420DNAHomo
sapiens 404aagccttgag aggtcttgaa 2040520DNAHomo sapiens
405aatacctgca aagccttgag 2040620DNAHomo sapiens 406tgcagttaaa
tacctgcaaa 2040720DNAHomo sapiens 407caacaacaag agagtgaaga
2040820DNAHomo sapiens 408ctgaattcaa aaccagggtg 2040920DNAHomo
sapiens 409atacctgcaa agccttgaga 2041020DNAHomo sapiens
410ttccccttag aaagctgaag 2041120DNAHomo sapiens 411ggagagctga
attcaaaacc 2041220DNAHomo sapiens 412gcagttaaat acctgcaaag
2041320DNAHomo sapiens 413gaagaatgca gttaaatacc 2041420DNAHomo
sapiens 414atgcagttaa atacctgcaa 2041520DNAHomo sapiens
415cattcccctt agaaagctga 2041620DNAHomo sapiens 416agagctgaat
tcaaaaccag 2041720DNAHomo sapiens 417gatgggagag ctgaattcaa
2041820DNAHomo sapiens 418tgatgggaga gctgaattca 2041920DNAHomo
sapiens 419actttgagct cacagtgtca 2042020DNAHomo sapiens
420gagtgaagaa tgcagttaaa 2042145DNAHomo sapiens 421gtgaagaatg
cagttaaata cctgcaaagc cttgagaggt cttga 4542245DNAHomo sapiens
422cagggatgcc atcgtttttg taactgtgca gggcagggcc atctg 4542345DNAHomo
sapiens 423gaccccaaca acaagagagt gaagaatgca gttaaatacc tgcaa
4542445DNAHomo sapiens 424agttaaatac ctgcaaagcc ttgagaggtc
ttgaagcctc ctcac 4542545DNAHomo sapiens 425tgaagaatgc agttaaatac
ctgcaaagcc ttgagaggtc ttgaa 4542645DNAHomo sapiens 426caagagagtg
aagaatgcag ttaaatacct gcaaagcctt gagag 4542745DNAHomo sapiens
427catctgttcg gaccccaaca acaagagagt gaagaatgca gttaa 4542845DNAHomo
sapiens 428ctgctgatgg gagagctgaa ttcaaaacca gggtgtctcc ctgag
4542945DNAHomo sapiens 429gaagaatgca gttaaatacc tgcaaagcct
tgagaggtct tgaag 4543045DNAHomo sapiens 430acttcaaggg agccattccc
cttagaaagc tgaagacgtg gtacc 4543145DNAHomo sapiens 431caccgcctgc
tgatgggaga gctgaattca aaaccagggt gtctc 4543245DNAHomo sapiens
432aagagagtga agaatgcagt taaatacctg caaagccttg agagg 4543345DNAHomo
sapiens 433caacaacaag agagtgaaga atgcagttaa atacctgcaa agcct
4543445DNAHomo sapiens 434acaagagagt gaagaatgca gttaaatacc
tgcaaagcct tgaga 4543545DNAHomo sapiens 435gtacttcaag ggagccattc
cccttagaaa gctgaagacg tggta 4543645DNAHomo sapiens 436ccgcctgctg
atgggagagc tgaattcaaa accagggtgt ctccc 4543745DNAHomo sapiens
437gtgtcaccgc ctgctgatgg gagagctgaa ttcaaaacca gggtg 4543845DNAHomo
sapiens 438agtgtcaccg cctgctgatg ggagagctga attcaaaacc agggt
4543945DNAHomo sapiens 439gctcagagag aagtgacttt gagctcacag
tgtcaccgcc tgctg 4544045DNAHomo sapiens 440accccaacaa caagagagtg
aagaatgcag ttaaatacct gcaaa 4544120DNAHomo sapiens 441gtatttgaaa
acagagtaaa 2044220DNAHomo sapiens 442caataagctg agccaatgaa
2044320DNAHomo sapiens 443tacttaagag gccaaataga 2044420DNAHomo
sapiens 444atgtatttga aaacagagta 2044520DNAHomo sapiens
445ttcatacagc aagtatggga 2044620DNAHomo sapiens 446ctgcagacaa
aatcaataaa 2044720DNAHomo sapiens 447tgcagacaaa atcaataaaa
2044820DNAHomo sapiens 448ggccaaatag atgaatggaa 2044920DNAHomo
sapiens 449aataagctga gccaatgaag 2045020DNAHomo sapiens
450aagaggccaa atagatgaat 2045120DNAHomo sapiens 451aaatagatga
atggaagaat 2045220DNAHomo sapiens 452aaacagagta aatacttaag
2045320DNAHomo sapiens 453agctggagtt atatatgtat 2045420DNAHomo
sapiens 454acctttgact tggtattata 2045520DNAHomo sapiens
455aaccttcagg gataaggaga 2045620DNAHomo sapiens 456gtgaaagact
acctttgact 2045720DNAHomo sapiens 457ctatggtgtg aaagactacc
2045820DNAHomo sapiens 458cactacggct ggctaatttt 2045920DNAHomo
sapiens 459ggagttatat atgtatttga 2046020DNAHomo sapiens
460atatcaatac agagactcaa 2046145DNAHomo sapiens 461gctggagtta
tatatgtatt tgaaaacaga gtaaatactt aagag 4546245DNAHomo sapiens
462ggtgaagatg attctcaata agctgagcca atgaagagcc tactc 4546345DNAHomo
sapiens 463tgaaaacaga gtaaatactt aagaggccaa atagatgaat ggaag
4546445DNAHomo sapiens 464aagctggagt tatatatgta tttgaaaaca
gagtaaatac ttaag 4546545DNAHomo sapiens 465ttgagaaata ttcttttcat
acagcaagta tgggacagca gtgtc 4546645DNAHomo sapiens 466gagcccagaa
agtggctgca gacaaaatca ataaaactaa tgtcc 4546745DNAHomo sapiens
467agcccagaaa gtggctgcag acaaaatcaa taaaactaat gtccc 4546845DNAHomo
sapiens 468agtaaatact taagaggcca aatagatgaa tggaagaatt ttagg
4546945DNAHomo sapiens 469gtgaagatga ttctcaataa gctgagccaa
tgaagagcct actct 4547045DNAHomo sapiens 470acagagtaaa tacttaagag
gccaaataga tgaatggaag aattt 4547145DNAHomo sapiens 471aatacttaag
aggccaaata gatgaatgga agaattttag gaact 4547245DNAHomo sapiens
472tatatatgta tttgaaaaca gagtaaatac ttaagaggcc aaata 4547345DNAHomo
sapiens 473tgacttggta ttataagctg gagttatata tgtatttgaa aacag
4547445DNAHomo sapiens 474atggtgtgaa agactacctt tgacttggta
ttataagctg gagtt 4547545DNAHomo sapiens 475tggcgtggtg ttgctaacct
tcagggataa ggagatctgt gccga 4547645DNAHomo sapiens 476aattcatgct
atggtgtgaa agactacctt tgacttggta ttata 4547745DNAHomo sapiens
477acaatcaaat tcatgctatg gtgtgaaaga ctacctttga cttgg 4547845DNAHomo
sapiens 478attacaggtg tgtgccacta cggctggcta atttttgtat tttta
4547945DNAHomo sapiens 479ttggtattat aagctggagt tatatatgta
tttgaaaaca gagta 4548045DNAHomo sapiens 480ccaaaaggca gttacatatc
aatacagaga ctcaaggtca ctaga 4548120DNAHomo sapiens 481ctgttttgtt
aatgaagaaa 2048220DNAHomo sapiens 482ttgtatataa atgtatttat
2048320DNAHomo sapiens 483tgttttgtta atgaagaaat 2048420DNAHomo
sapiens 484aattttggta aatatgtaca 2048520DNAHomo sapiens
485aaattttatg aatgacaaaa 2048620DNAHomo sapiens 486tttatggaat
attgtgcaaa 2048720DNAHomo sapiens 487ttactgtttt gttaatgaag
2048820DNAHomo sapiens 488ttcttgaatt agaaacacaa 2048920DNAHomo
sapiens 489cagttgctct taagagaata 2049020DNAHomo sapiens
490caacttcaaa agacaccaag 2049120DNAHomo sapiens 491tccaaaataa
attttatgaa 2049220DNAHomo sapiens 492gaactgaatt acgcataaga
2049320DNAHomo sapiens 493ggattttgtg acaaaccagg 2049420DNAHomo
sapiens 494tactgttttg ttaatgaaga 2049520DNAHomo sapiens
495tttggtaaat atgtacaaag 2049620DNAHomo sapiens 496ccaaaataaa
ttttatgaat 2049720DNAHomo sapiens 497ataatttaaa ttttggtaaa
2049820DNAHomo sapiens 498aaatgggtga actgaattac 2049920DNAHomo
sapiens 499ttcgggtcta tgtgactata 2050020DNAHomo sapiens
500actgttttgt taatgaagaa 2050145DNAHomo sapiens 501tatttgagtt
ttttactgtt ttgttaatga agaaattcct tttta 4550245DNAHomo sapiens
502tgtgactata tttttttgta tataaatgta tttatggaat attgt 4550345DNAHomo
sapiens 503atttgagttt tttactgttt tgttaatgaa gaaattcctt tttaa
4550445DNAHomo sapiens 504gttttttata atttaaattt tggtaaatat
gtacaaaggc acttc 4550545DNAHomo sapiens 505atatttttcc aaaataaatt
ttatgaatga caaaaaaaaa aaaaa 4550645DNAHomo sapiens 506ttgtatataa
atgtatttat ggaatattgt gcaaatgtta tttga 4550745DNAHomo sapiens
507tgttatttga gttttttact gttttgttaa tgaagaaatt ccttt 4550845DNAHomo
sapiens 508ttatgagcca gtcttttctt gaattagaaa cacaaacact gcctt
4550945DNAHomo sapiens 509ccgttgcact atggacagtt gctcttaaga
gaatatatat ttaaa 4551045DNAHomo sapiens 510cggactcggg ctgttcaact
tcaaaagaca ccaagtacca gtcgg 4551145DNAHomo sapiens 511tttttaaaat
atttttccaa aataaatttt atgaatgaca aaaaa 4551245DNAHomo sapiens
512tatatttaaa tgggtgaact gaattacgca taagaagcat gcact 4551345DNAHomo
sapiens 513tgtgatgagc agcatggatt ttgtgacaaa ccaggggaat gcaag
4551445DNAHomo sapiens 514gttatttgag ttttttactg ttttgttaat
gaagaaattc ctttt 4551545DNAHomo sapiens 515ttttataatt taaattttgg
taaatatgta caaaggcact tcggg 4551645DNAHomo sapiens 516ttttaaaata
tttttccaaa ataaatttta tgaatgacaa aaaaa 4551745DNAHomo sapiens
517tgatgttcgt tttttataat ttaaattttg gtaaatatgt acaaa 4551845DNAHomo
sapiens 518agagaatata tatttaaatg ggtgaactga attacgcata agaag
4551945DNAHomo sapiens 519tatgtacaaa ggcacttcgg gtctatgtga
ctatattttt ttgta 4552045DNAHomo sapiens 520ttatttgagt tttttactgt
tttgttaatg aagaaattcc ttttt 4552120DNAHomo sapiens 521tagctcctca
actcacctaa 2052220DNAHomo sapiens 522atgttttcct ataatataat
2052320DNAHomo sapiens 523ttttcctata atataataaa 2052420DNAHomo
sapiens 524ttcctataat ataataaata 2052520DNAHomo sapiens
525tgcatttgag gtcaagtaag 2052620DNAHomo sapiens 526attgattgtc
agctactaat 2052720DNAHomo sapiens 527aaatgaaaac atgtaataaa
2052820DNAHomo sapiens 528attgtgaagt acatattagg 2052920DNAHomo
sapiens 529gctttctgga gtgaagtata 2053020DNAHomo sapiens
530catttggtca agattttgaa 2053120DNAHomo sapiens 531ggcttatata
agctctaaga 2053220DNAHomo sapiens 532accagtgctg atcatttata
2053320DNAHomo sapiens 533ccatttaaca ggcaagtcca 2053420DNAHomo
sapiens 534aagtacatat taggaaaata 2053520DNAHomo sapiens
535tgtgtgtgtg tatgactaaa 2053620DNAHomo sapiens 536aagagggaga
agcatgaaaa 2053720DNAHomo sapiens 537gtgtatgact aaagagagaa
2053820DNAHomo sapiens 538gtatttccag tgcaattgta 2053920DNAHomo
sapiens 539caactctaat agtgcttaaa 2054020DNAHomo sapiens
540gtgtgtgtgt atgactaaag 2054145DNAHomo sapiens 541ggttcaaaat
gtctgtagct cctcaactca cctaatgttt atgag 4554245DNAHomo sapiens
542tgtcagctac taatgatgtt ttcctataat ataataaata tttat 4554345DNAHomo
sapiens 543cagctactaa tgatgttttc ctataatata ataaatattt atgta
4554445DNAHomo sapiens 544gctactaatg atgttttcct ataatataat
aaatatttat gtaga 4554545DNAHomo sapiens 545gagggtcttc ttacatgcat
ttgaggtcaa gtaagaagac atgaa 4554645DNAHomo sapiens 546tagtgcttaa
aaatcattga ttgtcagcta ctaatgatgt tttcc 4554745DNAHomo sapiens
547atgtgcattt ttgtgaaatg aaaacatgta ataaaaagta tatgt 4554845DNAHomo
sapiens 548agagagaatg tagatattgt gaagtacata ttaggaaaat atggg
4554945DNAHomo sapiens 549ctatggaatt gtcctgcttt ctggagtgaa
gtataagaag ggtgg 4555045DNAHomo sapiens 550ggaaaatatg ggttgcattt
ggtcaagatt ttgaatgctt cctga 4555145DNAHomo sapiens 551tctcagacgt
ttttcggctt atataagctc taagagaagc acttt 4555245DNAHomo sapiens
552gcagtgttca atcttaccag tgctgatcat ttatatgtca acgta 4555345DNAHomo
sapiens 553gctgaggaaa gtggcccatt taacaggcaa gtccaactca aggtc
4555445DNAHomo sapiens 554aatgtagata ttgtgaagta catattagga
aaatatgggt tgcat 4555545DNAHomo sapiens 555gtgtgtgtgt gtgtgtgtgt
gtgtgtatga ctaaagagag aatgt 4555645DNAHomo sapiens 556ctgggctgcc
atgtgaagag ggagaagcat gaaaaagcag ctacc 4555745DNAHomo sapiens
557tgtgtgtgtg tgtgtgtgta tgactaaaga gagaatgtag atatt 4555845DNAHomo
sapiens 558cctaacacag catgtgtatt tccagtgcaa ttgtaggggt gtgtg
4555945DNAHomo sapiens 559atgcttcctg acaatcaact ctaatagtgc
ttaaaaatca ttgat 4556045DNAHomo sapiens 560tgtgtgtgtg tgtgtgtgtg
tgtgtatgac taaagagaga atgta 4556120DNAHomo sapiens 561acctgcatta
atttaataaa 2056220DNAHomo sapiens 562aacttgccca aaccagtaaa
2056320DNAHomo sapiens 563atttgctcac atctagtaaa 2056420DNAHomo
sapiens 564cctttgccat ataatctaat 2056520DNAHomo sapiens
565atatagcaga tggaatgaat 2056620DNAHomo sapiens
566gcctttgcca tataatctaa 2056720DNAHomo sapiens 567gatttgcctt
tgccatataa 2056820DNAHomo sapiens 568aattttcatt tacaaagaga
2056920DNAHomo sapiens 569agtgtttctt atatagcaga 2057020DNAHomo
sapiens 570gctttctgtc aagtataaac 2057120DNAHomo sapiens
571catttggaaa tgtatgttaa 2057220DNAHomo sapiens 572ttattttagt
gtttcttata 2057320DNAHomo sapiens 573gtggtagcct acacacataa
2057420DNAHomo sapiens 574atgaggagat taacaagaaa 2057520DNAHomo
sapiens 575caattttgtc gccaaactaa 2057620DNAHomo sapiens
576tatatagcag atggaatgaa 2057720DNAHomo sapiens 577aaatgccact
aaattttaaa 2057820DNAHomo sapiens 578tctttcccat agcttttcat
2057920DNAHomo sapiens 579tatattcatg acctactggc 2058020DNAHomo
sapiens 580gtccagtgtc atagcataag 2058145DNAHomo sapiens
581attgtcactt tttgtacctg cattaattta ataaaatatt cttat 4558245DNAHomo
sapiens 582gcaaacagat taagtaactt gcccaaacca gtaaatagca gacct
4558345DNAHomo sapiens 583acttgctgct taatgatttg ctcacatcta
gtaaaacatg gagta 4558445DNAHomo sapiens 584tttattcctg atttgccttt
gccatataat ctaatgcttg tttat 4558545DNAHomo sapiens 585attttagtgt
ttcttatata gcagatggaa tgaatttgaa gttcc 4558645DNAHomo sapiens
586atttattcct gatttgcctt tgccatataa tctaatgctt gttta 4558745DNAHomo
sapiens 587attatattta ttcctgattt gcctttgcca tataatctaa tgctt
4558845DNAHomo sapiens 588cttaataatc agagtaattt tcatttacaa
agagaggtcg gtact 4558945DNAHomo sapiens 589atttttattt attttagtgt
ttcttatata gcagatggaa tgaat 4559045DNAHomo sapiens 590gaacttttgt
tttctgcttt ctgtcaagta taaacttcac tttga 4559145DNAHomo sapiens
591tctaaagata gtctacattt ggaaatgtat gttaaaagca cgtat 4559245DNAHomo
sapiens 592ctttgctatt tttatttatt ttagtgtttc ttatatagca gatgg
4559345DNAHomo sapiens 593cagctttaca attatgtggt agcctacaca
cataatctca tttca 4559445DNAHomo sapiens 594ggagctcata gtataatgag
gagattaaca agaaaatgta ttatt 4559545DNAHomo sapiens 595ttgtagtaga
tgttacaatt ttgtcgccaa actaaacttg ctgct 4559645DNAHomo sapiens
596tattttagtg tttcttatat agcagatgga atgaatttga agttc 4559745DNAHomo
sapiens 597ctgtcttttc tatttaaatg ccactaaatt ttaaattcat acctt
4559845DNAHomo sapiens 598tttgtttcta agttatcttt cccatagctt
ttcattatct ttcat 4559945DNAHomo sapiens 599gatatttgct gtctttatat
tcatgaccta ctggcatttg ctgaa 4560045DNAHomo sapiens 600tattattaca
atttagtcca gtgtcatagc ataaggatga tgcga 4560120DNAHomo sapiens
601attctgtcat aataaataaa 2060220DNAHomo sapiens 602tatcttatca
ttggaataaa 2060320DNAHomo sapiens 603gtgatggaga ctgcagtaaa
2060420DNAHomo sapiens 604ttctgtcata ataaataaaa 2060520DNAHomo
sapiens 605cttgtaggaa aacaacaaaa 2060620DNAHomo sapiens
606ataaaatgac attcaataaa 2060720DNAHomo sapiens 607cgtaaggtct
tgccaagaaa 2060820DNAHomo sapiens 608tcttgtagga aaacaacaaa
2060920DNAHomo sapiens 609aactggaggc actgatttaa 2061020DNAHomo
sapiens 610caatacaaaa gacctcaaaa 2061120DNAHomo sapiens
611tgcttctgca atcaaagtaa 2061220DNAHomo sapiens 612aatgacattc
aataaataaa 2061320DNAHomo sapiens 613atcattggaa taaaatgaca
2061420DNAHomo sapiens 614accaataatg caatacaaaa 2061520DNAHomo
sapiens 615atctgtatct tatcattgga 2061620DNAHomo sapiens
616atcttatcat tggaataaaa 2061720DNAHomo sapiens 617cagctgcttc
tgcaatcaaa 2061820DNAHomo sapiens 618gcaatacaaa agacctcaaa
2061920DNAHomo sapiens 619tcctactgta ttcaaggcaa 2062020DNAHomo
sapiens 620cagagccaca aactaatact 2062145DNAHomo sapiens
621aaaaaaaaaa gatatattct gtcataataa ataaaaatgc ataag 4562245DNAHomo
sapiens 622aagttttgta atctgtatct tatcattgga ataaaatgac attca
4562345DNAHomo sapiens 623ttttgttctc atttcgtgat ggagactgca
gtaaaggatt cttcc 4562445DNAHomo sapiens 624aaaaaaaaag atatattctg
tcataataaa taaaaatgca taaga 4562545DNAHomo sapiens 625aatacctgtg
catttcttgt aggaaaacaa caaaaggtaa ttatg 4562645DNAHomo sapiens
626tatcttatca ttggaataaa atgacattca ataaataaaa atgca 4562745DNAHomo
sapiens 627ggtcatggag atgtccgtaa ggtcttgcca agaaatattg ctgtt
4562845DNAHomo sapiens 628aaatacctgt gcatttcttg taggaaaaca
acaaaaggta attat 4562945DNAHomo sapiens 629actggaagcc aaaggaactg
gaggcactga tttaatgaat ttcct 4563045DNAHomo sapiens 630gttttaccaa
taatgcaata caaaagacct caaaatacct gtgca 4563145DNAHomo sapiens
631ggtggaaata gcagctgctt ctgcaatcaa agtaattcct actgt 4563245DNAHomo
sapiens 632ttatcattgg aataaaatga cattcaataa ataaaaatgc ataag
4563345DNAHomo sapiens 633tgtaatctgt atcttatcat tggaataaaa
tgacattcaa taaat 4563445DNAHomo sapiens 634actatgcaat gttttaccaa
taatgcaata caaaagacct caaaa 4563545DNAHomo sapiens 635actagaagtt
ttgtaatctg tatcttatca ttggaataaa atgac 4563645DNAHomo sapiens
636agttttgtaa tctgtatctt atcattggaa taaaatgaca ttcaa 4563745DNAHomo
sapiens 637tattggtgga aatagcagct gcttctgcaa tcaaagtaat tccta
4563845DNAHomo sapiens 638tgttttacca ataatgcaat acaaaagacc
tcaaaatacc tgtgc 4563945DNAHomo sapiens 639tgcaatcaaa gtaattccta
ctgtattcaa ggcaatgcaa atgca 4564045DNAHomo sapiens 640cattacccat
tgtaacagag ccacaaacta atactatgca atgtt 4564120DNAHomo sapiens
641ttgttcattt atttattgga 2064220DNAHomo sapiens 642ttattccaat
aaattgtcaa 2064320DNAHomo sapiens 643tattttctgg acactcaaac
2064420DNAHomo sapiens 644tttattggag aggcagcatt 2064520DNAHomo
sapiens 645accttggaga agtcacttat 2064620DNAHomo sapiens
646ttatttattt attttgttca 2064720DNAHomo sapiens 647ctctttcctg
tatcataaag 2064820DNAHomo sapiens 648ctgaggaaat gggtatgaat
2064920DNAHomo sapiens 649gaatgtgcct tgaacacaaa 2065020DNAHomo
sapiens 650ggacactcaa acacatcata 2065120DNAHomo sapiens
651ctgtatcata aaggattatt 2065220DNAHomo sapiens 652tcacttccga
gagtatgaga 2065320DNAHomo sapiens 653tctctggagc attctgaaaa
2065420DNAHomo sapiens 654ttatgccaga ggctaacaga 2065520DNAHomo
sapiens 655agtggcattg acttagttca 2065620DNAHomo sapiens
656tttctggaca ctcaaacaca 2065720DNAHomo sapiens 657gcattgcaca
gtgaaagaat 2065820DNAHomo sapiens 658gaccttggag aagtcactta
2065920DNAHomo sapiens 659tcacgttcac acacaagaaa 2066020DNAHomo
sapiens 660actttgctgt ttccagtggt 2066145DNAHomo sapiens
661ctttatttat ttattttgtt catttattta ttggagaggc agcat 4566245DNAHomo
sapiens 662agtgatacat gttttttatt ccaataaatt gtcaagacca cagga
4566345DNAHomo sapiens 663agatcttaag gtatatattt tctggacact
caaacacatc ataat 4566445DNAHomo sapiens 664tattttgttc atttatttat
tggagaggca gcattgcaca gtgaa 4566545DNAHomo sapiens 665gtttccagtg
gtatgacctt ggagaagtca cttatcctct tggag 4566645DNAHomo sapiens
666gttcccttga aagctttatt tatttatttt gttcatttat ttatt 4566745DNAHomo
sapiens 667tctccctcct aggaactctt tcctgtatca taaaggatta tttgc
4566845DNAHomo sapiens 668ggatgtgagg ttctgctgag gaaatgggta
tgaatgtgcc ttgaa 4566945DNAHomo sapiens 669tgaggaaatg ggtatgaatg
tgccttgaac acaaagctct gtcaa 4567045DNAHomo sapiens 670aggtatatat
tttctggaca ctcaaacaca tcataatgga ttcac 4567145DNAHomo sapiens
671cctaggaact ctttcctgta tcataaagga ttatttgctc agggg 4567245DNAHomo
sapiens 672tgaaagcatc ttcagtcact tccgagagta tgagattgcc attcg
4567345DNAHomo sapiens 673tctcagccct gcctttctct ggagcattct
gaaaacagat attct 4567445DNAHomo sapiens 674aagctggctt gtttcttatg
ccagaggcta acagatccaa tggga 4567545DNAHomo sapiens 675aggggccagg
atgacagtgg cattgactta gttcaaaact ctgag 4567645DNAHomo sapiens
676tcttaaggta tatattttct ggacactcaa acacatcata atgga 4567745DNAHomo
sapiens 677tttattggag aggcagcatt gcacagtgaa agaattctgg atatc
4567845DNAHomo sapiens 678tgtttccagt ggtatgacct tggagaagtc
acttatcctc ttgga 4567945DNAHomo sapiens 679aggtgccggg aaacttcacg
ttcacacaca agaaagtaaa acatg 4568045DNAHomo sapiens 680gaaattctag
ctctgacttt gctgtttcca gtggtatgac cttgg 4568120DNAHomo sapiens
681tatttgattt attaacttaa 2068220DNAHomo sapiens 682gaaaagtaat
atttattaaa 2068320DNAHomo sapiens 683actttgtata gttatgtaaa
2068420DNAHomo sapiens 684gaatacttga accataaaat 2068520DNAHomo
sapiens 685tcttggcaat aaattttgaa 2068620DNAHomo sapiens
686tttctgcttt agacttgaaa 2068720DNAHomo sapiens 687tatatttatt
gactcttgag 2068820DNAHomo sapiens 688tatgatgacg tacaagtagt
2068920DNAHomo sapiens 689gtgttgttct tggcaataaa 2069020DNAHomo
sapiens 690ctgatctaaa agggaataaa 2069120DNAHomo sapiens
691tacgacgtca gatgtttaaa 2069220DNAHomo sapiens 692aataatcaag
agccttaaaa 2069320DNAHomo sapiens 693gtatgaaaac atggaacagt
2069420DNAHomo sapiens 694tggttttatg atgacgtaca 2069520DNAHomo
sapiens 695ttctgcttta gacttgaaaa 2069620DNAHomo sapiens
696cttggcaata aattttgaaa 2069720DNAHomo sapiens 697tttaatctac
tgcatttagg 2069820DNAHomo sapiens 698tgtatagtta tgtaaataat
2069920DNAHomo sapiens 699atttatattt attgactctt 2070020DNAHomo
sapiens 700cttttcacca ttcgtacata 2070145DNAHomo sapiens
701attaatcact gtgtatattt gatttattaa cttaataatc aagag 4570245DNAHomo
sapiens 702ttggcaataa attttgaaaa gtaatattta ttaaattttt ttgta
4570345DNAHomo sapiens 703aatgtcaaaa gtagaacttt gtatagttat
gtaaataatt ctttt 4570445DNAHomo sapiens 704tctaataagc tagttgaata
cttgaaccat aaaatgtcca gtaag 4570545DNAHomo sapiens 705tctttgatgt
gttgttcttg gcaataaatt ttgaaaagta atatt 4570645DNAHomo sapiens
706tgtttgtttt ttgtttttct gctttagact tgaaaagaga caggc 4570745DNAHomo
sapiens 707gatcatagtt ttatttatat ttattgactc ttgagttgtt tttgt
4570845DNAHomo sapiens 708tttgtatatt ggttttatga tgacgtacaa
gtagttctgt atttg 4570945DNAHomo sapiens 709aaatgcatct ttgatgtgtt
gttcttggca ataaattttg aaaag 4571045DNAHomo sapiens 710cctttttcca
tgcagctgat ctaaaaggga ataaaaggct gcgca 4571145DNAHomo sapiens
711gatggaattt ttttgtacga cgtcagatgt ttaaaacacc ttcta 4571245DNAHomo
sapiens 712ttgatttatt aacttaataa tcaagagcct taaaacatca ttcct
4571345DNAHomo sapiens 713ttattaaatt tttttgtatg aaaacatgga
acagtgtggc ctctt 4571445DNAHomo sapiens 714gttgtttttg tatattggtt
ttatgatgac gtacaagtag ttctg 4571545DNAHomo sapiens 715gtttgttttt
tgtttttctg ctttagactt gaaaagagac aggca 4571645DNAHomo sapiens
716ctttgatgtg ttgttcttgg caataaattt tgaaaagtaa tattt 4571745DNAHomo
sapiens 717gatttgattt ttttttttaa tctactgcat ttagggagta ttcta
4571845DNAHomo sapiens 718tcaaaagtag aactttgtat agttatgtaa
ataattcttt tttat 4571945DNAHomo sapiens 719ttagatcata gttttattta
tatttattga ctcttgagtt gtttt 4572045DNAHomo sapiens 720tgtaaattct
gatttctttt caccattcgt acataatact gaacc 4572120DNAHomo sapiens
721cgtttcttta accttgtata 2072220DNAHomo sapiens 722taaatgaatg
aacgaataaa 2072320DNAHomo sapiens 723tcattcattt attcctttgt
2072420DNAHomo sapiens 724gtaaatgtgt acatattaaa 2072520DNAHomo
sapiens 725acccacgaat acgtatcaag 2072620DNAHomo sapiens
726gttttataaa atagtataaa 2072720DNAHomo sapiens 727caactgagtc
aaggagcaaa 2072820DNAHomo sapiens 728atgtgtacat attaaaggaa
2072920DNAHomo sapiens 729ttctttaacc ttgtataaat 2073020DNAHomo
sapiens 730attttctacg tttctttaac 2073120DNAHomo sapiens
731cagttttata aaatagtata 2073220DNAHomo sapiens 732gcacaggcag
aacaaatgaa 2073320DNAHomo sapiens 733tcaggctgaa aacaatggag
2073420DNAHomo sapiens 734taaaattgct tacccacgaa 2073520DNAHomo
sapiens 735gtcaggctga aaacaatgga 2073620DNAHomo sapiens
736aaatgtgtac atattaaagg 2073720DNAHomo sapiens 737cagtaactgt
caggctgaaa 2073820DNAHomo sapiens 738gtattctcgg atagttgcta
2073920DNAHomo sapiens 739tctcacacaa attcaccaaa 2074020DNAHomo
sapiens 740ttgttttgct tggtcattca 2074145DNAHomo sapiens
741aatgtttatt ttctacgttt ctttaacctt gtataaatta ttcag 4574245DNAHomo
sapiens 742ggcagaacaa atgaataaat gaatgaacga ataaaaattt tgacc
4574345DNAHomo sapiens 743ggtcaaaatt tttattcatt catttattcc
tttgttttgc ttggt 4574445DNAHomo sapiens 744tgaaagtgca tttttgtaaa
tgtgtacata ttaaaggaag cactc 4574545DNAHomo sapiens 745agtataaaat
tgcttaccca cgaatacgta tcaaggtctt aagga 4574645DNAHomo sapiens
746aaacagctga aaacagtttt ataaaatagt ataaaattgc ttacc 4574745DNAHomo
sapiens 747tgaggggtag gaggtcaact gagtcaagga gcaaagccaa gaacc
4574845DNAHomo sapiens 748agtgcatttt tgtaaatgtg tacatattaa
aggaagcact ctgta 4574945DNAHomo sapiens 749gtttattttc tacgtttctt
taaccttgta taaattattc agtaa 4575045DNAHomo sapiens 750aaaaaccaaa
tgtttatttt ctacgtttct ttaaccttgt ataaa 4575145DNAHomo sapiens
751taaaacagct gaaaacagtt ttataaaata gtataaaatt gctta 4575245DNAHomo
sapiens 752gagtgaggct gccttgcaca ggcagaacaa atgaataaat gaatg
4575345DNAHomo sapiens 753attattcagt aactgtcagg ctgaaaacaa
tggagtattc tcgga 4575445DNAHomo sapiens 754ttttataaaa
tagtataaaa
ttgcttaccc acgaatacgt atcaa 4575545DNAHomo sapiens 755aattattcag
taactgtcag gctgaaaaca atggagtatt ctcgg 4575645DNAHomo sapiens
756aaagtgcatt tttgtaaatg tgtacatatt aaaggaagca ctctg 4575745DNAHomo
sapiens 757cttgtataaa ttattcagta actgtcaggc tgaaaacaat ggagt
4575845DNAHomo sapiens 758gctgaaaaca atggagtatt ctcggatagt
tgctattttt gtaaa 4575945DNAHomo sapiens 759aggcggagaa gttcctctca
cacaaattca ccaaagatcc tggcc 4576045DNAHomo sapiens 760cattcattta
ttcctttgtt ttgcttggtc attcagaggc aaggt 4576120DNAHomo sapiens
761tcatgcgaaa agaacctaca 2076220DNAHomo sapiens 762aaatgtcaga
agcttacaga 2076320DNAHomo sapiens 763aaacatatga aacatgaaaa
2076420DNAHomo sapiens 764cagttcctta tctaccaaat 2076520DNAHomo
sapiens 765tcctggtaca gaccatatta 2076620DNAHomo sapiens
766ttccttatct accaaattct 2076720DNAHomo sapiens 767ttcctggtac
agaccatatt 2076820DNAHomo sapiens 768aagtatatac attcagctga
2076920DNAHomo sapiens 769cattacaacc agacagttga 2077020DNAHomo
sapiens 770agggacctaa aacctagtaa 2077120DNAHomo sapiens
771ctctggagga attcaatgat 2077220DNAHomo sapiens 772taaacatatg
aaacatgaaa 2077320DNAHomo sapiens 773gatctgaaca acattgtgaa
2077420DNAHomo sapiens 774tcagttcctt atctaccaaa 2077520DNAHomo
sapiens 775ataattcaca gggacctaaa 2077620DNAHomo sapiens
776cgaggtctaa agtatataca 2077720DNAHomo sapiens 777gaaatgtcag
aagcttacag 2077820DNAHomo sapiens 778agctgttgac tggaagaaca
2077920DNAHomo sapiens 779aaattctccg aggtctaaag 2078020DNAHomo
sapiens 780aatgtgattg gtctgttgga 2078145DNAHomo sapiens
781atttcagtcc atcattcatg cgaaaagaac ctacagagaa ctgcg 4578245DNAHomo
sapiens 782ctgaacaaca ttgtgaaatg tcagaagctt acagatgacc atgtt
4578345DNAHomo sapiens 783gaactgcggt tacttaaaca tatgaaacat
gaaaatgtga ttggt 4578445DNAHomo sapiens 784acagatgacc atgttcagtt
ccttatctac caaattctcc gaggt 4578545DNAHomo sapiens 785tggaagaaca
ttgtttcctg gtacagacca tattaaccag cttca 4578645DNAHomo sapiens
786gatgaccatg ttcagttcct tatctaccaa attctccgag gtcta 4578745DNAHomo
sapiens 787ctggaagaac attgtttcct ggtacagacc atattaacca gcttc
4578845DNAHomo sapiens 788attctccgag gtctaaagta tatacattca
gctgacataa ttcac 4578945DNAHomo sapiens 789atgctgaact ggatgcatta
caaccagaca gttgatattt ggtca 4579045DNAHomo sapiens 790gctgacataa
ttcacaggga cctaaaacct agtaatctag ctgtg 4579145DNAHomo sapiens
791ttacacctgc aaggtctctg gaggaattca atgatgtgta tctgg 4579245DNAHomo
sapiens 792agaactgcgg ttacttaaac atatgaaaca tgaaaatgtg attgg
4579345DNAHomo sapiens 793catctcatgg gggcagatct gaacaacatt
gtgaaatgtc agaag 4579445DNAHomo sapiens 794tacagatgac catgttcagt
tccttatcta ccaaattctc cgagg 4579545DNAHomo sapiens 795atacattcag
ctgacataat tcacagggac ctaaaaccta gtaat 4579645DNAHomo sapiens
796atctaccaaa ttctccgagg tctaaagtat atacattcag ctgac 4579745DNAHomo
sapiens 797tctgaacaac attgtgaaat gtcagaagct tacagatgac catgt
4579845DNAHomo sapiens 798gatgcataat ggccgagctg ttgactggaa
gaacattgtt tcctg 4579945DNAHomo sapiens 799agttccttat ctaccaaatt
ctccgaggtc taaagtatat acatt 4580045DNAHomo sapiens 800catatgaaac
atgaaaatgt gattggtctg ttggacgttt ttaca 4580120DNAHomo sapiens
801ctgctgtgca gaatcctatt 2080220DNAHomo sapiens 802gctgtgcaga
atcctatttt 2080320DNAHomo sapiens 803ttaaagtcag tttaggtaat
2080420DNAHomo sapiens 804ctgtgcagaa tcctatttta 2080520DNAHomo
sapiens 805gtttacatat acccagtatc 2080620DNAHomo sapiens
806attttgttat tacttgcctg 2080720DNAHomo sapiens 807taactgggat
gccgtgttat 2080820DNAHomo sapiens 808tgttattact tgcctggaac
2080920DNAHomo sapiens 809tttctgctgt gcagaatcct 2081020DNAHomo
sapiens 810cgtgttattt tgttattact 2081120DNAHomo sapiens
811ttttaaagtc agtttaggta 2081220DNAHomo sapiens 812tgctgtgcag
aatcctattt 2081320DNAHomo sapiens 813ggatgccgtg ttattttgtt
2081420DNAHomo sapiens 814tttaaagtca gtttaggtaa 2081520DNAHomo
sapiens 815taaagtcagt ttaggtaata 2081620DNAHomo sapiens
816tctgctgtgc agaatcctat 2081720DNAHomo sapiens 817atatacccag
tatctttgca 2081820DNAHomo sapiens 818agaatcctat tttatatttt
2081920DNAHomo sapiens 819ggttgttgta gcagcttaac 2082020DNAHomo
sapiens 820cccagtatct ttgcacaaac 2082145DNAHomo sapiens
821tctggcttta tttttctgct gtgcagaatc ctattttata ttttt 4582245DNAHomo
sapiens 822tggctttatt tttctgctgt gcagaatcct attttatatt tttta
4582345DNAHomo sapiens 823cctattttat attttttaaa gtcagtttag
gtaataaact ttatt 4582445DNAHomo sapiens 824ggctttattt ttctgctgtg
cagaatccta ttttatattt tttaa 4582545DNAHomo sapiens 825ctcctacctc
ttcatgttta catataccca gtatctttgc acaaa 4582645DNAHomo sapiens
826ctgggatgcc gtgttatttt gttattactt gcctggaacc atgtg 4582745DNAHomo
sapiens 827ccgtgcacgc agcattaact gggatgccgt gttattttgt tatta
4582845DNAHomo sapiens 828gatgccgtgt tattttgtta ttacttgcct
ggaaccatgt gggta 4582945DNAHomo sapiens 829gtctctggct ttatttttct
gctgtgcaga atcctatttt atatt 4583045DNAHomo sapiens 830cattaactgg
gatgccgtgt tattttgtta ttacttgcct ggaac 4583145DNAHomo sapiens
831atcctatttt atatttttta aagtcagttt aggtaataaa cttta 4583245DNAHomo
sapiens 832ctggctttat ttttctgctg tgcagaatcc tattttatat ttttt
4583345DNAHomo sapiens 833acgcagcatt aactgggatg ccgtgttatt
ttgttattac ttgcc 4583445DNAHomo sapiens 834tcctatttta tattttttaa
agtcagttta ggtaataaac tttat 4583545DNAHomo sapiens 835ctattttata
ttttttaaag tcagtttagg taataaactt tatta 4583645DNAHomo sapiens
836ctctggcttt atttttctgc tgtgcagaat cctattttat atttt 4583745DNAHomo
sapiens 837cctcttcatg tttacatata cccagtatct ttgcacaaac caggg
4583845DNAHomo sapiens 838atttttctgc tgtgcagaat cctattttat
attttttaaa gtcag 4583945DNAHomo sapiens 839cctctgggtc cccctggttg
ttgtagcagc ttaactgtat ctgga 4584045DNAHomo sapiens 840tcatgtttac
atatacccag tatctttgca caaaccaggg gttgg 4584120DNAHomo sapiens
841atattgctgt atctacttta 2084220DNAHomo sapiens 842tgtttgttaa
atcaaattag 2084320DNAHomo sapiens 843tttatctaaa tgcaaataag
2084420DNAHomo sapiens 844attttccttt gtaatgtatt 2084520DNAHomo
sapiens 845tatcagcaca atctacgaag 2084620DNAHomo sapiens
846agcttaactg ataaacagaa 2084720DNAHomo sapiens 847gttgttgttg
ttcttagaca 2084820DNAHomo sapiens 848gttgttgttc ttagacaagt
2084920DNAHomo sapiens 849tctgtattta agaaacttaa 2085020DNAHomo
sapiens 850ttattttcct ttgtaatgta 2085120DNAHomo sapiens
851taactgataa acagaatatt 2085220DNAHomo sapiens 852acattctggg
cacaaacaca 2085320DNAHomo sapiens 853gtgatctgct tttatctaaa
2085420DNAHomo sapiens 854cagacccgtc aacaaattaa 2085520DNAHomo
sapiens 855ggagctgttt agaaacttaa 2085620DNAHomo sapiens
856accattgggt ttaaatcata 2085720DNAHomo sapiens 857ggagaatcta
agcattttag 2085820DNAHomo sapiens 858ccttgctgac atccaaatag
2085920DNAHomo sapiens 859aaattaagaa ataataacaa 2086020DNAHomo
sapiens 860ttttaaatta agaaataata 2086145DNAHomo sapiens
861tttttttttt ttggtatatt gctgtatcta ctttaacttc cagaa 4586245DNAHomo
sapiens 862gtttctgtgg aattctgttt gttaaatcaa attagctggt ctctg
4586345DNAHomo sapiens 863tgtgggtgat ctgcttttat ctaaatgcaa
ataaggatgt gttct 4586445DNAHomo sapiens 864tttataaata gacttatttt
cctttgtaat gtattggcct tttag 4586545DNAHomo sapiens 865gagtcgaatg
ttctctatca gcacaatcta cgaagaatca agcag 4586645DNAHomo sapiens
866cttcagtaca taataagctt aactgataaa cagaatattt agaaa 4586745DNAHomo
sapiens 867cagctttttg ttattgttgt tgttgttctt agacaagtgc ctcct
4586845DNAHomo sapiens 868ctttttgtta ttgttgttgt tgttcttaga
caagtgcctc ctggt 4586945DNAHomo sapiens 869tatcagcata gcctttctgt
atttaagaaa cttaagcagc cgggc 4587045DNAHomo sapiens 870tttttataaa
tagacttatt ttcctttgta atgtattggc ctttt 4587145DNAHomo sapiens
871agtacataat aagcttaact gataaacaga atatttagaa aggtg 4587245DNAHomo
sapiens 872gatcccggaa atttaacatt ctgggcacaa acacaaaagt gatga
4587345DNAHomo sapiens 873aatgagtgaa tgtgggtgat ctgcttttat
ctaaatgcaa ataag 4587445DNAHomo sapiens 874gcagaatctc aacttcagac
ccgtcaacaa attaagaaac tggag 4587545DNAHomo sapiens 875ggaggagaga
atcgtggagc tgtttagaaa cttaatgaaa agtgc 4587645DNAHomo sapiens
876gtgagacttg ggcttaccat tgggtttaaa tcatagggac ctagg 4587745DNAHomo
sapiens 877aataggaagg tttaaggaga atctaagcat tttagacttt ttttt
4587845DNAHomo sapiens 878cattgcactt tttaaccttg ctgacatcca
aatagaagat aggac 4587945DNAHomo sapiens 879cctaggtttc tttttaaatt
aagaaataat aacaattaaa gggca 4588045DNAHomo sapiens 880aagccctagg
tttcttttta aattaagaaa taataacaat taaag 4588120DNAHomo sapiens
881agcttgaact gaggagtaaa 2088220DNAHomo sapiens 882cctttgcaac
atcctcagaa 2088320DNAHomo sapiens 883ttctttccaa agataccaaa
2088420DNAHomo sapiens 884ttattttatt acaaacttca 2088520DNAHomo
sapiens 885tatttatact tattataaaa 2088620DNAHomo sapiens
886catttcagac aaaatgctaa 2088720DNAHomo sapiens 887atgaaggaga
agctcttaaa 2088820DNAHomo sapiens 888attttgtgtt gatcattatt
2088920DNAHomo sapiens 889ttcatcgagt acagagaaaa 2089020DNAHomo
sapiens 890ttactgggaa gacgtgtaac 2089120DNAHomo sapiens
891tcattgaagc tcagaatcag 2089220DNAHomo sapiens 892ttccattctt
aatgtgaaaa 2089320DNAHomo sapiens 893tgaaggatac tgccagaagt
2089420DNAHomo sapiens 894cacaagagtc aacattaaaa 2089520DNAHomo
sapiens 895aattatttat acttattata 2089620DNAHomo sapiens
896ttcgtgcttc tccttatgaa 2089720DNAHomo sapiens 897tattttatta
caaacttcaa 2089820DNAHomo sapiens 898tattacaaac ttcaagatta
2089920DNAHomo sapiens 899ctcttaaagt tgatatctta 2090020DNAHomo
sapiens 900ttccaaagat accaaataaa 2090145DNAHomo sapiens
901acttctaaag aagttagctt gaactgagga gtaaaagtgt gtaca 4590245DNAHomo
sapiens 902aatacacata tttgtccttt gcaacatcct cagaaggcca atcat
4590345DNAHomo sapiens 903acgaatcttt ataatttctt tccaaagata
ccaaataaac ttcag 4590445DNAHomo sapiens 904tgtaattcac tttatttatt
ttattacaaa cttcaagatt attta 4590545DNAHomo sapiens 905gtgaaaaaaa
gtaattattt atacttatta taaaaagtat ttgaa 4590645DNAHomo sapiens
906aaggccaatc attgtcattt cagacaaaat gctaagaagt ttgga 4590745DNAHomo
sapiens 907gatcctgaaa atgagatgaa ggagaagctc ttaaaagagt actta
4590845DNAHomo sapiens 908agttgatatc ttaatatttt gtgttgatca
ttatttccat tctta 4590945DNAHomo sapiens 909ttttgcacac tgtgtttcat
cgagtacaga gaaaacaaac atttt 4591045DNAHomo sapiens 910aaaaattaga
atattttact gggaagacgt gtaactcttt gggtt 4591145DNAHomo sapiens
911actgccagaa gtgtttcatt gaagctcaga atcagagatt tcatg 4591245DNAHomo
sapiens 912tgtgttgatc attatttcca ttcttaatgt gaaaaaaagt aatta
4591345DNAHomo sapiens 913tggaagcacc atgtttgaag gatactgcca
gaagtgtttc attga 4591445DNAHomo sapiens 914ataaatgtaa cttttcacaa
gagtcaacat taaaaaataa attat 4591545DNAHomo sapiens 915aatgtgaaaa
aaagtaatta tttatactta ttataaaaag tattt 4591645DNAHomo sapiens
916catattcatc gatgtttcgt gcttctcctt atgaaactcc agcta 4591745DNAHomo
sapiens 917gtaattcact ttatttattt tattacaaac ttcaagatta tttaa
4591845DNAHomo sapiens 918tcactttatt tattttatta caaacttcaa
gattatttaa gtgaa 4591945DNAHomo sapiens 919tgttttcatc taattctctt
aaagttgata tcttaatatt ttgtg 4592045DNAHomo sapiens 920atctttataa
tttctttcca aagataccaa ataaacttca gtgtt 4592120DNAHomo sapiens
921aatttgactt agccactaac 2092220DNAHomo sapiens 922gatattaata
atatagttaa 2092320DNAHomo sapiens 923ctgtgaatgc acatattaaa
2092420DNAHomo sapiens 924gttttctatt tcctcttaag 2092520DNAHomo
sapiens 925aaatagcact aagaagttat 2092620DNAHomo sapiens
926ccaatcccga tccaaatcat 2092720DNAHomo sapiens 927ctatttagag
aatgcttaag 2092820DNAHomo sapiens 928cagtttgcat attgcctaaa
2092920DNAHomo sapiens 929ctcgaattca aagtatcaaa 2093020DNAHomo
sapiens 930atctgtgaat gcacatatta 2093120DNAHomo sapiens
931tttgtgggaa aagaattgaa 2093220DNAHomo sapiens 932attgaccatg
ttctgcaaaa 2093320DNAHomo sapiens 933gattcttcat tgcaagtgaa
2093420DNAHomo sapiens 934gatgtcaaat agcactaaga 2093520DNAHomo
sapiens 935gtatacaggg agagtgagat 2093620DNAHomo sapiens
936gttgctatga gtcaaggagt 2093720DNAHomo sapiens 937tagttgaaat
gtccccttaa 2093820DNAHomo sapiens 938ctctgtgcca aaccttttat
2093920DNAHomo sapiens 939ctctgtctag aaataccata 2094020DNAHomo
sapiens 940ggtttcaaga aatgaggtga 2094145DNAHomo sapiens
941gagatcagaa ttttaaattt gacttagcca ctaactagcc atgta 4594245DNAHomo
sapiens 942gagagtatta atattgatat taataatata gttaatagta
atatt 4594345DNAHomo sapiens 943tgcttacagt gttatctgtg aatgcacata
ttaaatgtct atgtt 4594445DNAHomo sapiens 944ggattttttt ttcctgtttt
ctatttcctc ttaagtacac cttca 4594545DNAHomo sapiens 945attcaatctg
atgtcaaata gcactaagaa gttattgtgc cttat 4594645DNAHomo sapiens
946aatgcttaag ggattccaat cccgatccaa atcataattt gttct 4594745DNAHomo
sapiens 947ttagttagat attttctatt tagagaatgc ttaagggatt ccaat
4594845DNAHomo sapiens 948aggttaaatt gattgcagtt tgcatattgc
ctaaatttaa acttt 4594945DNAHomo sapiens 949tatcacatcg gtatcctcga
attcaaagta tcaaagtaca attta 4595045DNAHomo sapiens 950tatgcttaca
gtgttatctg tgaatgcaca tattaaatgt ctatg 4595145DNAHomo sapiens
951tatacatggc agagttttgt gggaaaagaa ttgaatgaaa agtca 4595245DNAHomo
sapiens 952atttcacttt ttgttattga ccatgttctg caaaattgca gttac
4595345DNAHomo sapiens 953ggtggacagg gcatggattc ttcattgcaa
gtgaaggagc ctccc 4595445DNAHomo sapiens 954tatcaaattc aatctgatgt
caaatagcac taagaagtta ttgtg 4595545DNAHomo sapiens 955aagagagatt
ttcttgtata cagggagagt gagataactt attgt 4595645DNAHomo sapiens
956aatgtctatg ttcttgttgc tatgagtcaa ggagtgtaac cttct 4595745DNAHomo
sapiens 957gtatcccctt atgtttagtt gaaatgtccc cttaacttga tataa
4595845DNAHomo sapiens 958gatgatttgt aacttctctg tgccaaacct
tttataaaca taaat 4595945DNAHomo sapiens 959atgaaaaata atgatctctg
tctagaaata ccatagacca tatat 4596045DNAHomo sapiens 960cacagaaaca
ttgctggttt caagaaatga ggtgatccta ttatc 4596120DNAHomo sapiens
961agttgctgtt taaaatagaa 2096220DNAHomo sapiens 962ctgtttaaaa
tagaaataaa 2096320DNAHomo sapiens 963ggcatcagcg atgaactaaa
2096420DNAHomo sapiens 964aatatcctaa gactaacaaa 2096520DNAHomo
sapiens 965gttgctgttt aaaatagaaa 2096620DNAHomo sapiens
966aaaatagaaa taaaattgaa 2096720DNAHomo sapiens 967ctgtgaagct
cacaacctaa 2096820DNAHomo sapiens 968ttgaagacta aagacctaaa
2096920DNAHomo sapiens 969tcctaagact aacaaaggca 2097020DNAHomo
sapiens 970ggacatttcc aagctgttag 2097120DNAHomo sapiens
971atgtttccat ggttaccatg 2097220DNAHomo sapiens 972tagttgctgt
ttaaaataga 2097320DNAHomo sapiens 973aaaattgaag actaaagacc
2097420DNAHomo sapiens 974agctgttagg gacatttcca 2097520DNAHomo
sapiens 975gaggacgtgt atgatctcat 2097620DNAHomo sapiens
976ttttaggtga gggttggtaa 2097720DNAHomo sapiens 977agctgacatc
attgcctcaa 2097820DNAHomo sapiens 978aaatctcaaa atatcctaag
2097920DNAHomo sapiens 979aagctgttag ttgctgttta 2098020DNAHomo
sapiens 980tccttgtaat attccctttt 2098145DNAHomo sapiens
981catttccaag ctgttagttg ctgtttaaaa tagaaataaa attga 4598245DNAHomo
sapiens 982ccaagctgtt agttgctgtt taaaatagaa ataaaattga agact
4598345DNAHomo sapiens 983acattggaca gcttgggcat cagcgatgaa
ctaaaggaaa aactg 4598445DNAHomo sapiens 984gctaccaaat ctcaaaatat
cctaagacta acaaaggcag ctgtg 4598545DNAHomo sapiens 985atttccaagc
tgttagttgc tgtttaaaat agaaataaaa ttgaa 4598645DNAHomo sapiens
986tgttagttgc tgtttaaaat agaaataaaa ttgaagacta aagac 4598745DNAHomo
sapiens 987gagcaccatg ttttcctgtg aagctcacaa cctaaaaggc ctggc
4598845DNAHomo sapiens 988aaaatagaaa taaaattgaa gactaaagac
ctaaaaaaaa aaaaa 4598945DNAHomo sapiens 989ccaaatctca aaatatccta
agactaacaa aggcagctgt gtctg 4599045DNAHomo sapiens 990ggtcctagct
gttagggaca tttccaagct gttagttgct gttta 4599145DNAHomo sapiens
991aggagtgggg tggttatgtt tccatggtta ccatgggtgt ggatg 4599245DNAHomo
sapiens 992acatttccaa gctgttagtt gctgtttaaa atagaaataa aattg
4599345DNAHomo sapiens 993gtttaaaata gaaataaaat tgaagactaa
agacctaaaa aaaaa 4599445DNAHomo sapiens 994catggggcgg gtcctagctg
ttagggacat ttccaagctg ttagt 4599545DNAHomo sapiens 995cctccggagt
gtatggagga cgtgtatgat ctcatgtacc agtgc 4599645DNAHomo sapiens
996ccttgtaata ttccctttta ggtgagggtt ggtaaggggt tggta 4599745DNAHomo
sapiens 997tgtgaagatg ctgaaagctg acatcattgc ctcaagcgac attga
4599845DNAHomo sapiens 998tctgagcacg ctaccaaatc tcaaaatatc
ctaagactaa caaag 4599945DNAHomo sapiens 999gttagggaca tttccaagct
gttagttgct gtttaaaata gaaat 45100045DNAHomo sapiens 1000agtcacaaag
agatgtcctt gtaatattcc cttttaggtg agggt 45100120DNAArtificial
SequenceSynthetic polynucleotide 1001gagtaggaca taccagctta
20100219DNAArtificial SequenceSynthetic polynucleotide
1002agagttctgt ggaagtcta 19100319DNAArtificial SequenceSynthetic
polynucleotide 1003agagttctgt ggaagtcta 19100419DNAArtificial
SequenceSynthetic polynucleotide 1004agagttctgt ggaagtcta
19100519DNAArtificial SequenceSynthetic polynucleotide
1005acagcaaatt ccatcgtgt 19100620DNAArtificial SequenceSynthetic
polynucleotide 1006ctggtaaagt ggatattgtt 20100719DNAArtificial
SequenceSynthetic polynucleotide 1007agagttctgt ggaagtcta 19
* * * * *